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HLA class II polymorphisms determine responses to bacterial superantigens.
Martin Llewelyn1, Shiranee Sriskandan, Mark Peakman
1Department of Infectious Diseases, Faculty of Medicine, Imperial College, Department of Immunology, Guy's, Kings and St. Thomas' School of Medicine, London, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|January 22, 2004
Summary
Human leukocyte antigen (HLA) polymorphisms influence how superantigens bind to immune cells. This binding variation affects T cell responses, explaining differences in disease severity from bacterial infections.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Microbial superantigens trigger excessive immune responses implicated in diseases like toxic shock syndrome.
- The role of human leukocyte antigen (HLA) polymorphisms in superantigenicity has been largely overlooked.
- Superantigen presentation to T cells is not MHC-restricted, suggesting potential influence of HLA variations.
Purpose of the Study:
- To investigate the impact of HLA class II polymorphisms on superantigen binding.
- To explore the functional consequences of differential superantigen-HLA interactions on T cell activation.
Main Methods:
- Studied binding of streptococcal and staphylococcal superantigens to various HLA class II alleles.
- Utilized human T cells and Vbeta8.2 transgenic mouse cells to assess T cell activation.
- Analyzed T cell proliferation, cytokine production, and T cell receptor Vbeta repertoire.
Main Results:
- Allelic differences in HLA class II, specifically DQ alpha-chains, affect superantigen binding affinity.
- HLA-DQA1*01 alpha-chains exhibit greater binding to streptococcal pyrogenic exotoxin A than DQA1*03/05.
- Differential HLA-DQ binding leads to quantitative and qualitative variations in T cell proliferation, cytokine release, and Vbeta repertoire.
Conclusions:
- HLA polymorphisms significantly influence superantigen binding and subsequent T cell responses.
- This mechanism helps explain the diverse clinical outcomes observed in infections caused by toxigenic bacteria.
- Highlights the importance of considering host genetic factors in understanding superantigen-mediated diseases.