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Alloreactive T-cell clones identify multiple HLA-DQw3 variants.
E M Mickelson1, S A Masewicz, G T Nepom
1Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Human Immunology
|January 1, 1991
Summary
Human Leukocyte Antigen (HLA)-DQw3 alloantigens have functional variants. T-cell clones reveal distinct recognition sites on DQ beta chains and suggest alpha-beta chain interactions influence T-cell responses to HLA-DQ molecules.
Area of Science:
- Immunology
- Human Leukocyte Antigen (HLA) research
- Molecular genetics
Background:
- HLA-DQw3 is a broad alloantigen with known subdivisions (DQw7, DQw8, DQw9).
- Understanding structural variations in HLA-DQw3 is crucial for characterizing T-cell responses.
Purpose of the Study:
- To characterize functionally relevant structural polymorphisms within the HLA-DQw3 alloantigen family.
- To investigate T-cell recognition patterns of different HLA-DQw3 variants.
Main Methods:
- Generation of DQw3-reactive T-cell clones.
- Analysis of T-cell recognition of six distinct DQw3 variants.
- Comparison of DQB and DQA gene sequences.
Main Results:
- T-cell clones identified distinct functional variants of DQw3.
- Specific recognition sites were proposed on the DQ beta chain for some clones.
- Allo-recognition appeared to be determined by interactions between DQ alpha and DQ beta chains for other clones.
Conclusions:
- T cells recognize specific alloepitopes on HLA class II molecules.
- T-cell recognition of HLA-DQ molecules can involve individual chains or their interactions.
- These findings highlight the diversity of T-cell responses to HLA-DQ and its implications for alloreactivity and peptide binding.