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T cell cross-reactivity and conformational changes during TCR engagement
Jean K Lee1, Guillaume Stewart-Jones, Tao Dong
1Human Immunology Unit, Medical Research Council, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DS, England, UK.
The Journal of Experimental Medicine
|December 8, 2004
Summary
T cells recognize HIV peptides with surprising specificity. Despite structural differences, T cell receptors bind variants after initial contact, impacting vaccine design for viruses like HIV.
Area of Science:
- Immunology
- Virology
- Structural Biology
Background:
- T cells exhibit inherent cross-reactivity but also fine specificity in antigen recognition.
- This specificity allows viruses like human immunodeficiency virus (HIV) to escape immune control through mutation.
Purpose of the Study:
- To investigate the paradox of T cell cross-reactivity versus fine specificity.
- To analyze T cell receptor recognition of human immunodeficiency virus (HIV) gag epitope variants bound to human histocompatibility leukocyte antigen (HLA)-A2.
Main Methods:
- Analysis of 171 variant peptides for HLA-A2 binding and T cell recognition.
- Structural analysis of recognized peptide variants bound to HLA-A2.
- T cell receptor (TCR) binding kinetics assessment.
Main Results:
- Most variant peptides bound HLA-A2, but only one-third were recognized.
- A recognized variant (SLYNTVATL) displayed significant structural differences when bound to HLA-A2.
- TCR recognition suggested a conserved conformation within the TCR-peptide-MHC complex, despite initial structural variations.
Conclusions:
- T cell receptor-peptide-MHC interactions involve conformational changes post-initial antigen contact.
- Understanding these fine specificity mechanisms is crucial for designing effective vaccines against viruses with mutable genomes, such as HIV.