Mutually Exclusive T-Cell Receptor Induction and Differential Susceptibility to Human Immunodeficiency Virus Type 1 Mutational Escape Associated with a Two-Amino-Acid Difference between HLA Class I Subtypes
| Autor: | Photini Kiepiela, Madhu Vajpayee, William H. Hildebrand, Margaret E. Feeney, Richard A. Kaslow, Christian Brander, Yanhua Tang, Nicole Frahm, Eric S. Rosenberg, Montiago X. LaBute, Alisdair Leslie, Paul A. Goepfert, Senica Chetty, Hayley Crawford, Florencia Pereyra, Bruce D. Walker, Mathias Lichterfeld, Marcus Altfeld, Stanley K. Mui, Toshiyuki Miura, Todd M. Allen, Xu G. Yu, Philip J. R. Goulder, Rachel L. Allgaier, Katja Pfafferott, Katie L. Williams |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Immunology
Receptors Antigen T-Cell Epitopes T-Lymphocyte Gene Products gag HIV Infections Human leukocyte antigen CD8-Positive T-Lymphocytes Biology medicine.disease_cause Microbiology Epitope Virus Species Specificity Virology medicine Humans Allele Alleles Genetics Mutation Immunodominant Epitopes Histocompatibility Antigens Class I T-cell receptor Amino Acid Substitution Insect Science HIV-1 Pathogenesis and Immunity Viral disease CD8 |
| Zdroj: | Journal of Virology. 81:1619-1631 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01580-06 |
| Popis: | The relative contributions of HLA alleles and T-cell receptors (TCRs) to the prevention of mutational viral escape are unclear. Here, we examined human immunodeficiency virus type 1 (HIV-1)-specific CD8 + T-cell responses restricted by two closely related HLA class I alleles, B*5701 and B*5703, that differ by two amino acids but are both associated with a dominant response to the same HIV-1 Gag epitope KF11 (KAFSPEVIPMF). When this epitope is presented by HLA-B*5701, it induces a TCR repertoire that is highly conserved among individuals, cross-recognizes viral epitope variants, and is rarely associated with mutational escape. In contrast, KF11 presented by HLA-B*5703 induces an entirely different, more heterogeneous TCR β-chain repertoire that fails to recognize specific KF11 escape variants which frequently arise in clade C-infected HLA-B*5703 + individuals. These data show the influence of HLA allele subtypes on TCR selection and indicate that extensive TCR diversity is not a prerequisite to prevention of allowable viral mutations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|