Recognition of mycobacterial HSP65 in association with HLA-DR4 is not sufficient for autoreactivity.
The mycobacterial heat shock protein 65, class II major histocompatibility complex molecule HLA-DR4, and T cells have been implicated in autoimmunity. However, there has been no direct demonstration of the recognition of the heat shock protein 65 by T cells in association with HLA-DR4. In this study, we established T cell lines and a large number of T cell clones from healthy subjects vaccinated with killed mycobacteria. Among these subjects, three were HLA-DR4 positive, and the T cell lines and clones from these subjects responded to the mycobacterial heat shock protein 65. HLA-restriction studies were done with well-characterized anti-HLA class I, anti-HLA-DR, and anti-HLA-DQ antibodies. Only anti-HLA-DR antibodies inhibited the antigen-induced response of the T cell lines and clones to heat shock protein 65. When HLA-DR-typed allogeneic cells were used as antigen-presenting cells, the T cell clones from only one of the individuals were found to be HLA-DR4 restricted. To identify the epitopes recognized by these T cell clones, synthetic peptides were synthesized covering the entire sequence of mycobacterial heat shock protein 65. When tested with the heat shock protein 65-reactive T cell clones, peptides from five different regions of heat shock protein 65 stimulated the T cell clones in association with HLA-DR4. However, it is difficult to predict the role of HLA-DR4-restricted mycobacterial heat shock protein 65 peptides in autoimmunity from our studies, because the T cell clones were established from a healthy donor, and the peptides belonged to the regions that do not share sequence homology between the mycobacterial and human heat shock protein 65 or other proteins.
Mustafa
A S
AS
Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait.
D000942:Antigens, Bacterial / Q000276:immunology*; D015551:Autoimmunity; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology*; D015804:HLA-DR4 Antigen / Q000276:immunology*; D006801:Humans; D009161:Mycobacterium / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D015804:HLA-DR4 Antigen; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins