Drug Hypersensitivity: How Drugs Stimulate T Cells via Pharmacological Interaction with Immune Receptors

International Archives of Allergy and Immunology

Volumn 168, Issue 1, 2015, Pages 13-24

  Pichler, Werner J ^a   Adam, Jacqueline ^a   Watkins, Stephen ^c   Wuillemin, Natascha ^b   Yun, James ^d   Yerly, Daniel ^b  

^a ADR AC GmbH   (Switzerland)

^b UNIVERSITY OF BERN   (Switzerland)

^c OREGON STATE UNIVERSITY   (United States)

^d ROYAL PRINCE ALFRED HOSPITAL   (Australia)

Author keywords

Allo reactivity; Costimulation; p i concept; p i HLA; p i TCR

Indexed keywords

ABACAVIR; CARBAMAZEPINE; HLA ANTIGEN; HLA B15 ANTIGEN; HLA B57 ANTIGEN; HLA DRB1 ANTIGEN; SULFANILAMIDE DERIVATIVE; T LYMPHOCYTE RECEPTOR; LYMPHOCYTE ANTIGEN RECEPTOR;

ALLELE; ANTIGEN PRESENTING CELL; DELAYED HYPERSENSITIVITY; DENDRITIC CELL; DRESS SYNDROME; DRUG HYPERSENSITIVITY; DRUG INTERACTION; DRUG RECEPTOR BINDING; HUMAN; IMMUNITY; MEMORY T LYMPHOCYTE; MONOCYTE; PREDICTIVE VALUE; PRIORITY JOURNAL; REVIEW; STEVENS JOHNSON SYNDROME; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; ADVERSE DRUG REACTION; IMMUNOLOGY; LYMPHOCYTE ACTIVATION;

DRUG HYPERSENSITIVITY; DRUG-RELATED SIDE EFFECTS AND ADVERSE REACTIONS; HLA ANTIGENS; HUMANS; HYPERSENSITIVITY, DELAYED; LYMPHOCYTE ACTIVATION; RECEPTORS, ANTIGEN, T-CELL; T-LYMPHOCYTES;

EID: 84946751276     PISSN: 10182438     EISSN: 14230097     Source Type: Journal    
DOI: 10.1159/000441280     Document Type: Review

References (68)

1. Demoly P, Adkinson NF, Brockow K, Castells M, Chiriac AM, Greenberger PA, Khan DA, Lang DM, Park HS, Pichler W, Sanchez-Borges M, Shiohara T, Thong BY: International consensus on drug allergy. Allergy 2014; 69: 420-437.
2. Pichler WJ: Adverse side-effects to biological agents. Allergy 2006; 61: 912-920.
3. Landsteiner K, Jacobs J: Studies on the sensitization of animals with simple chemical compounds. J Exp Med 1936; 64: 625-639.
4. Whitaker P, Meng X, Lavergne SN, El-Ghaiesh S, Monshi M, Earnshaw C, Peckham D, Gooi J, Conway S, Pirmohamed M, Jenkins RE, Naisbitt DJ, Park BK: Mass spectrometric characterization of circulating and functional antigens derived from piperacillin in patients with cystic fibrosis. J Immunol 2011; 187: 200-211.
5. Aiba S: Maturation of dendritic cells induced by cytokines and haptens. Tohoku J Exp Med 1998; 184: 159-172.
6. Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C: A critical role for p38 mitogenactivated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-Aα, and contact sensitizers. J Immunol 2001; 166: 3837-3845.
7. Martin SF: Contact dermatitis: from pathomechanisms to immunotoxicology. Exp Dermatol 2012; 21: 382-389.
8. Schnyder B, Mauri-Hellweg D, Zanni M, Bettens F, Pichler WJ: Direct, MHC-dependent presentation of the drug sulfamethoxazole to human alphabeta T cell clones. J Clin Invest 1997; 100: 136-141.
9. Zanni MP, von Greyerz S, Schnyder B, Brander KA, Frutig K, Hari Y, Valitutti S, Pichler WJ: HLA-restricted, processing-And metabolism-independent pathway of drug recognition by human alpha beta T lymphocytes. J Clin Invest 1998; 102: 1591-1598.
10. Pichler WJ: Pharmacological interaction of drugs with antigen-specific immune receptors: the p-i concept. Curr Opin Allergy Clin Immunol 2002; 2: 301-305.
11. Pichler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, Spanou Z, Zawodniak A, Gerber B: Pharmacological interaction of drugs with immune receptors: the p-i concept. Allergol Int 2006; 55: 17-25.
12. Pichler WJ: Delayed drug hypersensitivity reactions. Ann Intern Med 2003; 139: 683-693.
13. Kowalski ML, Asero R, Bavbek S, Blanca M, Blanca-Lopez N, Bochenek G, Brockow K, Campo P, Celik G, Cernadas J, Cortellini G, Gomes E, Nizankowska-Mogilnicka E, Romano A, Szczeklik A, Testi S, Torres MJ, Wohrl S, Makowska J: Classification and practical approach to the diagnosis and management of hypersensitivity to nonsteroidal anti-inflammatory drugs. Allergy 2013; 68: 1219-1232.
14. McNeil BD, Pundir P, Meeker S, Han L, Undem BJ, Kulka M, Dong X: Identification of a mast-cell-specific receptor crucial for pseudo-Allergic drug reactions. Nature 2015; 519: 237-241.
15. Adam J, Pichler WJ, Yerly D: Delayed drug hypersensitivity: models of T-cell stimulation. Br J Clin Pharmacol 2011; 71: 701-707.
16. Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte C, Maxwell D, James I, Christiansen FT: Association between presence of HLA-B 5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002; 359: 727-732.
17. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT: Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004; 428: 486.
18. Hung SI, Chung WH, Liou LB, Chu CC, Lin M, Huang HP, Lin YL, Lan JL, Yang LC, Hong HS, Chen MJ, Lai PC, Wu MS, Chu CY, Wang KH, Chen CH, Fann CS, Wu JY, Chen YT: HLA-B 5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proc Natl Acad Sci USA 2005; 102: 4134-4139.
19. Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP; DILIGEN Study; International SAE Consortium: HLA-B 5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009; 41: 816-819.
20. Chang FR, Liu H, Irwanto A, et al: HLAB 13: 01 and the dapsone hypersensitivity syndrome. N Engl J Med 2013; 369: 1620-1628.
21. Pavlos R, Mallal S, Ostrov D, Buus S, Metushi I, Peters B, Phillips E: T cell-mediated hypersensitivity reactions to drugs. Annu Rev Med 2015; 66: 439-454.
22. Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jagel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A; PREDICT-1 Study Team: HLA-B 5701 screening for hypersensitivity to abacavir. N Engl J Med 2008; 358: 568-579.
23. McCormack M, Alfirevic A, Bourgeois S, Farrell JJ, Kasperavičiute D, Carrington M, Sills GJ, Marson T, Jia X, de Bakker PI, Chinthapalli K, Molokhia M, Johnson MR, O'Connor GD, Chaila E, Alhusaini S, Shianna KV, Radtke RA, Heinzen EL, Walley N, Pandolfo M, Pichler W, Park BK, Depondt C, Sisodiya SM, Goldstein DB, Deloukas P, Delanty N, Cavalleri GL, Pirmohamed M: HLA-A 3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med 2011; 364: 1134-1143.
24. Genin E, Chen DP, Hung SI, Sekula P, Schumacher M, Chang PY, Tsai SH, Wu TL, Bellon T, Tamouza R, Fortier C, Toubert A, Charron D, Hovnanian A, Wolkenstein P, Chung WH, Mockenhaupt M, Roujeau JC: HLA-A 31: 01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-Analysis. Pharmacogenomics J 2014; 14: 281-288.
25. Singer JB, Lewitzky S, Leroy E, et al: A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nat Genet 2010; 42: 711-714.
26. Vitezica ZG, Milpied B, Lonjou C, et al: HLADRB1 01 associated with cutaneous hypersensitivity induced by nevirapine and efavirenz. AIDS 2008; 22: 540-541.
27. Yang CW, Hung SI, Juo CG, Lin YP, Fang WH, Lu IH, Chen ST, Chen YT: HLA-B 1502 bound peptides: implications for the pathogenesis of carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol 2007; 120: 870-877.
28. Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z, Bharadwaj M, Miles JJ, Kjer-Nielsen L, Gras S, Williamson NA, Burrows SR, Purcell AW, Rossjohn J, McCluskey J: Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 2012; 486: 554-558.
29. Ostrov DA, Grant BJ, Pompeu YA, Sidney J, Harndahl M, Southwood S, Oseroff C, Lu S, Jakoncic J, de Oliveira CA, Yang L, Mei H, Shi L, Shabanowitz J, English AM, Wriston A, Lucas A, Phillips E, Mallal S, Grey HM, Sette A, Hunt DF, Buus S, Peters B: Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire. Proc Natl Acad Sci USA 2012; 109: 9959-9964.
30. Norcross MA, Luo S, Lu L, Boyne MT, Gomarteli M, Rennels AD, Woodcock J, Margulies DH, McMurtrey C, Vernon S, Hildebrand WH, Buchli R: Abacavir induces loading of novel self-peptides into HLA-B 57: 01: an autoimmune model for HLA-Associated drug hypersensitivity. AIDS 2012; 26:F21-F29.
31. Yun J, Adam J, Yerly D, Pichler WJ: Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA. Allergy 2012; 67: 1338-1346.
32. Illing PT, Vivian JP, Purcell AW, Rossjohn J, McCluskey J: Human leukocyte antigen-Associated drug hypersensitivity. Curr Opin Immunol 2013; 25: 81-89.
33. Ko TM, Chung WH, Wei CY, Shih HY, Chen JK, Lin CH, Chen YT, Hung SI: Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome. J Allergy Clin Immunol 2011; 128: 1266-1276.
34. Wei CY, Chung WH, Huang HW, Chen YT, Hung SI: Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome. J Allergy Clin Immunol 2012; 129: 1562-1569.
35. Adam J, Eriksson KK, Schnyder B, Fontana S, Pichler WJ, Yerly D: Avidity determines Tcell reactivity in abacavir hypersensitivity. Eur J Immunol 2012; 42: 1706-1716.
36. Yun J, Marcaida MJ, Eriksson KK, Jamin H, Fontana S, Pichler WJ, Yerly D: Oxypurinol directly and immediately activates the drugspecific T cells via the preferential use of HLA-B 58: 01. J Immunol 2014; 192: 2984-2993.
37. Wuillemin N, Adam J, Fontana S, Krahenbuhl S, Pichler WJ, Yerly D: HLA haplotype determines hapten or p-i T cell reactivity to flucloxacillin. J Immunol 2013; 190: 4956-4964.
38. Winkler K, Winter A, Rueckert C, Uchanska-Ziegler B, Alexiev U: Natural MHC class I polymorphism controls the pathway of peptide dissociation from HLA-B27 complexes. Biophys J 2007; 93: 2743-2755.
39. Baratin M, Bonin K, Daniel C: Frontline: peripheral priming of alloreactive T cells by the direct pathway of allorecognition. Eur J Immunol 2004; 34: 3305-3314.
40. Adam J, Wuillemin N, Watkins S, Jamin H, Eriksson K, Villiger P, Fontana S, Pichler WJ, Yerly D: Abacavir induced T cell reactivity represents an allo-immune reaction. PLoS One 2014; 9:e95339.
41. Golshayan D, Wyss JC, Buckland M, Hernandez-Fuentes M, Lechler RI: Differential role of naive and memory CD4 T-cell subsets in primary alloresponses. Am J Transplant 2010; 10: 1749-1759.
42. Macedo C, Orkis EA, Popescu I, et al: Contribution of naive and memory T-cell populations to the human alloimmune response. Am J Transplant 2009; 9: 2057-2066.
43. Lucas A, Lucas M, Strhyn A, Keane NM, McKinnon E, Pavlos R, Moran EM, Meyer-Pannwitt V, Gaudieri S, D'Orsogna L, Kalams S, Ostrov DA, Buus S, Peters B, Mallal S, Phillips E: Abacavir-reactive memory T cells are present in drug naive individuals. PLoS One 2015; 10:e0117160.
44. Felix NJ, Allen PM: Specificity of T-cell alloreactivity. Nat Rev Immunol 2007; 7: 942-953.
45. Wucherpfennig KW, Allen PM, Celada F, Cohen IR, De Boer R, Garcia KC, Goldstein B, Greenspan R, Hafler D, Hodgkin P, Huseby ES, Krakauer DC, Nemazee D, Perelson AS, Pinilla C, Strong RK, Sercarz EE: Polyspecificity of T cell and B cell receptor recognition. Semin Immunol 2007; 19: 216-224.
46. von Greyerz S, Bultemann G, Schnyder K, Burkhart C, Lotti B, Hari Y, Pichler WJ: Degeneracy and additional alloreactivity of drug-specific human aαβ + T cell clones. Int Immunol 2001; 13: 877-885.
47. Correia O, Delgado L, Barbosa IL, Domingues JC, Azevedo R, Vaz CP, Pimentel P: CD8+ lymphocytes in the blister fluid of severe acute cutaneous graft-versus-host disease: further similarities with toxic epidermal necrolysis. Dermatology 2001; 203: 212-216.
48. Takeda H, Mitsuhashi Y, Kondo S, Kato Y, Tajima K: Toxic epidermal necrolysis possibly linked to hyperacute graft-versus-host disease after allogeneic bone marrow transplantation. J Dermatol 1997; 24: 635-641.
49. Friedman HZ, Arias AM, Catchatourian R, Fretzin DF: Toxic epidermal necrolysis following bone marrow transplantation. Cutis 1984; 34: 158-162.
50. Jeanmonod P, Hubbuch M, Grunhage F, Meiser A, Rass K, Schilling MK, Kollmar O: Graft-versus-host disease or toxic epidermal necrolysis: diagnostic dilemma after liver transplantation. Transpl Infect Dis 2012; 14: 422-426.
51. Azukizawa H, Itami S: Animal models of toxic epidermal necrolysis; in Pichler WJ (ed): Drug Hypersensitivity. Basel, Karger, 2007, pp 129-139.
52. von Greyerz S, Zanni M, Frutig K, Schnyder B, Pichler WJ: Interaction of sulfonamide-derivatives with the TCR of sulfamethoxazole specific aαβ + T cell clones. J Immunol 1999; 162: 595-602.
53. Schmid DA, Depta JP, Luthi M, Pichler WJ: Transfection of drug specific T cell receptors into hybridoma cells: tools to monitor drug binding to TCR and to evaluate cross-reactivity to related compounds. Mol Pharmacol 2006; 70: 356-365.
54. Depta JP, Altznauer F, Gamerdinger K, Burkhart C, Weltzien HU, Pichler WJ: Drug interaction with T-cell receptors: T-cell receptor density determines degree of cross-reactivity. J Allergy Clin Immunol 2004; 113: 519-527.
55. Burkhart C, Britschgi M, Strasser I, Depta JP, von Greyerz S, Barnaba V, Pichler WJ: Noncovalent presentation of sulfamethoxazole to human CD4+ T cells is independent of distinct human leucocyte antigen-bound peptides. Clin Exp Allergy 2002; 32: 1635-1643.
56. Zanni MP, von Greyerz S, Schnyder B, Wendland T, Pichler WJ: Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific aα/β + T cell clones. Int Immunol 1998; 10: 507-515.
57. Watkins S, Pichler WJ: Activating interactions of sulfanilamides with T cell receptors. Open J Immunol 2013; 3: 139-157.
58. Watkins S, Pichler WJ: Sulfamethoxazole induces a switch mechanism in T cell receptors containing TCRVβ20-1, altering pHLA recognition. PLoS One 2013; 8:e76211.
59. Pichler WJ, Watkins S: Interaction of small molecules with specific immune receptors: the p-i concept and its consequences. Curr Immunol Rev 2014; 10: 7-18.
60. Schnyder B, Burkhart C, Schnyder-Frutig K, von Greyerz S, Naisbitt D, Pirmohamed M, Park K, Pichler WJ: Recognition of sulfamethoxazole and its reactive metabolites by drug specific T cells from allergic individuals. J Immunol 2000; 164: 6647-6654.
61. Elsheikh A, Lavergne SN, Castrejon JL, Farrell J, Wang H, Sathish J, Pichler WJ, Park BK, Naisbitt DJ: Drug antigenicity, immunogenicity, and costimulatory signaling: evidence for formation of a functional antigen through immune cell metabolism. J Immunol 2010; 185: 6448-6460.
62. Kohler J, Hartmann U, Grimm R, Pflugfelder U, Weltzien HU: Carrier-independent hapten recognition and promiscuous MHC restriction by CD4 T cells induced by trinitrophenylated peptides. J Immunol 1997; 158: 591-597.
63. Schnyder B, Adam J, Rauch A, Thurnheer MC, Pichler WJ: HLA-B 57: 01 + abacavir-naive individuals have specific T cells but no patch test reactivity. J Allergy Clin Immunol 2013; 132: 756-758.
64. Strom BL, Schinnar R, Apter AJ, Margolis DJ, Lautenbach E, Hennessy S, Bilker WB, Pettitt D: Absence of cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics. N Engl J Med 2003; 349: 1628-1635.
65. Gonzalez-Martin G, Yanez CG, Gonzalez-Contreras L, Labarca J: Adverse drug reactions (ADRs) in patients with HIV infection: a prospective study. Int J Clin Pharmacol Ther 1999; 37: 34-40.
66. Lin D, Tucker MJ, Rieder MJ: Increased adverse drug reactions to antimicrobials and anticonvulsants in patients with HIV infection. Ann Pharmacother 2006; 40: 1594-1601.
67. Jeffries M, Bruner G, Glenn S, Sadanandan P, Carson CW, Harley JB, Sawalha AH: Sulpha allergy in lupus patients: a clinical perspective. Lupus 2008; 17: 202-205.
68. Watkins S, Pichler WJ: T cell receptor variable β20-1 harbors a nucleotide binding pocket in the CDR2β loop. Open J Immunol 2013; 3: 165-174.