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A single CTL clone can recognize a naturally processed HIV-1 epitope presented by two different HLA class I molecules
H Tomiyama1, N Yamada, H Komatsu
1Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Japan.
European Journal of Immunology
|September 29, 2000
Summary
A single human immunodeficiency virus-1 (HIV-1) epitope is presented by two different HLA class I molecules. This finding demonstrates cross-recognition by a single T cell receptor (TCR), offering insights into immune response diversity.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Cytotoxic T Lymphocytes (CTLs) recognize viral peptides presented by MHC class I molecules.
- Previous studies suggested a single peptide could be recognized by CTLs restricted to two MHC class I alleles, but direct evidence was lacking.
- The mechanism of single peptide presentation by multiple MHC class I molecules and its implications for T cell recognition remained unclear.
Purpose of the Study:
- To provide direct evidence for the presentation of a single peptide by two distinct MHC class I molecules.
- To investigate whether a single CTL clone can recognize a peptide presented by both HLA-B35 and HLA-B51.
- To elucidate the cross-recognition capabilities of T cell receptors (TCRs) for different HLA-peptide complexes.
Main Methods:
- Utilized HIV-1 recombinant vaccinia virus to infect target cells.
- Isolated and purified the naturally processed HIV-B35-SF2-24 epitope from HLA-B*3501 and HLA-B*5101 molecules.
- Employed tetrameric complexes of HLA-B*3501-SF2-24 to analyze CTL clone recognition.
- Performed TCR analysis to confirm the clonal origin of the CTLs.
Main Results:
- Demonstrated that the HIV-B35-SF2-24 epitope is naturally processed and presented by both HLA-B*3501 and HLA-B*5101 molecules.
- Showed that a single CTL clone recognizes the same peptide presented by both HLA-B35 and HLA-B51.
- Evidence suggests that the TCR of this CTL clone cross-recognizes the structure of both HLA class I-peptide complexes.
Conclusions:
- This study provides the first direct evidence for a single peptide being presented by two different MHC class I molecules (HLA-B*3501 and HLA-B*5101).
- A single CTL clone can recognize this peptide regardless of whether it is presented by HLA-B35 or HLA-B51, indicating TCR cross-reactivity.
- These findings have significant implications for understanding viral immune evasion strategies and designing effective T cell-based immunotherapies.