Preferential presentation of herpes simplex virus T-cell antigen by HLA DQA1*0501/DQB1*0201 in comparison to HLA DQA1*0201/DQB1*0201
| Autor: | William W. Kwok, Aimee N. Ekstrom, Patricia Byers, Matthew L. Johnson, David M. Koelle |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
CD4-Positive T-Lymphocytes
musculoskeletal diseases endocrine system diseases Protein Conformation Herpesvirus 2 Human Immunology Receptors Antigen T-Cell Peptide binding Human leukocyte antigen Biology HLA-DQ alpha-Chains HLA-DQ Antigens HLA-DQ HLA-DQ beta-Chains Humans Immunology and Allergy Amino Acids skin and connective tissue diseases Antigens Viral Alleles Cell Line Transformed Antigen Presentation Herpes simplex virus protein vmw65 HLA-DQB1 HLA-DQ Antigen T-cell receptor HLA-DQ2 nutritional and metabolic diseases Herpes Simplex Virus Protein Vmw65 General Medicine Virology Peptides |
| Zdroj: | Human Immunology. 53:195-205 |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/s0198-8859(97)00034-7 |
| Popis: | The HLA DQA1 locus is polymorphic. Haplotypes containing HLA DQA1*0501, but not HLA DQA1*0201, together with HLA DQB1*0201 are associated with Grave's disease and celiac sprue. In this report, we demonstrate a functional correlate of DQA1 polymorphism. T cells infiltrating a herpes simplex virus (HSV) lesion from a HLA DQ 2,7 individual yielded a virus-specific CD4+ clone restricted by DQ2. Presentation of viral peptide and protein segregated with DQA1 allele, because cell lines bearing DQA1*0501/DQB1*0201 heterodimers presented antigen in proliferation and cytotoxicity assays much more efficiently than cell lines bearing DQA1*0201/DQB1*0201. Binding of viral peptide to cell lines bearing DQA1*0201, in comparison to DQA1*0501, was only moderately reduced and may not explain this effect. Truncation and substitution analyses of peptide binding and T-cell activation were performed to determine which viral peptide residues contacting TCR might therefore be presented in an altered conformation by DQA1*0201/DQB1*0201. Residues 432, 435, 437, 438, and 440 (position P1, P4, P6, P7, and P9) contributed to DQ2 binding, whereas residues 431, 433, 434, and 436 (positions P 1, P2, P3, and P5) contributed to TCR contact. Differential presentation of peptide by HLA DQ2 heterodimers varying at the DQA1 locus may have relevance to host defense and the pathogenesis of HLA DQ2-associated autoimmune diseases. |
| Databáze: | OpenAIRE |
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