DQw3 variants defined by cloned alloreactive T cells

Area of Science:

• Immunogenetics
• Molecular immunology
• Human Leukocyte Antigen (HLA) complex research

Background:

• Human Leukocyte Antigen (HLA) class II molecules play a crucial role in immune responses.
• The serologically defined alloantigen DQw3 exhibits polymorphism, necessitating detailed characterization.
• Understanding HLA polymorphism is vital for transplantation and autoimmune disease research.

Purpose of the Study:

• To investigate the polymorphism of HLA class II molecules expressing the DQw3 alloantigen.
• To identify and characterize distinct DQw3-associated determinants using cloned T lymphocytes.
• To correlate T-cell defined determinants with molecular polymorphisms in the DQ beta gene.

Main Methods:

• Utilized cloned proliferative T lymphocytes (T cell clones) for specific antigen recognition.
• Tested T cell clone reactivity against a panel of HLA-D homozygous cells.
• Employed monoclonal antibody inhibition assays and DNA hybridization with a DQ beta probe.

Main Results:

• Two T cell clones, IG9 and IC3, were specific for DQw3 but recognized distinct determinants.
• Clone IG9 recognized determinants on various DR haplotypes, while clone IC3 recognized a subset of DR4-associated determinants.
• Monoclonal anti-DQ antibodies blocked clone reactivity, confirming DQ molecule association. DNA hybridization revealed DQ beta gene polymorphisms (DQw"3.1" and "3.2") correlating with T-cell defined determinants.

Conclusions:

• Demonstrated functionally relevant recognition sites on DQw3+ molecules defined by T-cell reactivity.
• Established a correlation between T-cell defined DQw3 determinants and structural polymorphisms in the DQ beta gene.
• Highlighted the utility of cloned T cells and molecular analysis in dissecting HLA polymorphism.