Related Experiment Videos
Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide
J M Brooks1, R J Murray, W A Thomas
1Department of Cancer Studies, University of Birmingham, UK.
The Journal of Experimental Medicine
|September 1, 1993
Summary
Different subtypes of the HLA-B27 allele can present the same arthritogenic peptide, providing evidence for an immunological basis of ankylosing spondylitis. This study demonstrates functional overlap in cytotoxic T lymphocyte (CTL) epitope presentation among disease-associated B27 subtypes.
Area of Science:
- Immunology
- Genetics
Background:
- Ankylosing spondylitis is strongly associated with multiple HLA-B27 subtypes.
- A proposed immunological mechanism involves cytotoxic T lymphocyte (CTL) responses to a shared "arthritogenic" peptide presented by these subtypes.
- This hypothesis requires overlapping peptide-binding repertoires among different B27 molecules.
Purpose of the Study:
- To provide direct evidence that different disease-related HLA-B27 alleles can present the same immunodominant peptide.
- To investigate the peptide binding and presentation capabilities of HLA-B27 subtypes using Epstein-Barr virus (EBV) as a model system.
Main Methods:
- Utilized Epstein-Barr virus (EBV)-specific cytotoxic T lymphocyte (CTL) clones from donors positive for HLA-B27 subtypes (B27.05, B27.02, B27.04).
- Assessed CTL recognition of EBV-transformed B cell lines and targets expressing individual EBV proteins via recombinant vaccinia virus vectors.
- Performed peptide sensitization assays to identify specific viral peptides recognized by CTLs.
Main Results:
- While initially showing subtype-specific restriction, EBV-specific CTL clones recognized a common viral nuclear antigen, Epstein-Barr nuclear antigen (EBNA)3C, across B27.05, B27.02, and B27.04 subtypes.
- Identified a shared immunodominant viral peptide (RRIYDLIEL from EBNA3C) recognized by CTLs restricted by B27.05, B27.02, and B27.04.
- A distinct B27.04-restricted CTL response targeted an EBV latent membrane protein 2 (LMP2) epitope, indicating some subtype-specific presentation.
Conclusions:
- Demonstrates a functional overlap in the presentation of at least one immunodominant CTL epitope among different disease-associated HLA-B27 subtypes.
- Provides the first direct evidence supporting the hypothesis that shared peptide presentation contributes to the association between HLA-B27 and ankylosing spondylitis.
- Suggests that the peptide-binding grooves of B27.05, B27.02, and B27.04 can accommodate the same arthritogenic peptide (RRIYDLIEL).