Identification of mycobacterial peptide epitopes recognized by CD4+ T cells in association with multiple major histocompatibility complex class II molecules.
The mycobacterial 18-, 28-, and 65-kDa proteins are recognized by T cells in association with multiple class II HLA-DR molecules of the major histocompatibility complex (MHC). To identify the epitopes recognized by T cells in association with multiple HLA-DR molecules, we established CD4+ T cell lines and clones and tested them with overlapping synthetic peptides corresponding to the entire amino acid sequence of the 18- and 65-kDa antigens and to the carboxy terminus of the 28-kDa antigen. The T cell lines established against the 18-kDa antigen recognized three different epitopes, one of which was recognized in the presence of antigen-presenting cells from several allogeneic donors. The 65-kDa antigen-reactive T cell lines responded to nine different peptides, two of which were promiscuous with respect to MHC restriction. The T cell clones responding to the 28-kDa antigen proliferated in response to a single peptide from the carboxy terminus. This peptide was recognized by T cell clones in association with HLA-DRw53, which is coexpressed in individuals expressing HLA-DR4, HLA-DR7, and HLA-DR9. The T cells activated in response to the mycobacterial antigen from vaccinated donors belonged to the protective Th1 subset; hence, the peptides recognized in association with multiple HLA-DR molecules should be useful in subunit vaccines against mycobacterial diseases.
Mustafa
A S
AS
Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait.
D000942:Antigens, Bacterial / Q000032:analysis* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000276:immunology; D015809:HLA-DR7 Antigen / Q000276:immunology; D059845:HLA-DRB4 Chains; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D009161:Mycobacterium / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
D000942:Antigens, Bacterial; D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; C050610:HLA-DR53; D015809:HLA-DR7 Antigen; C038988:HLA-DR9 antigen; D059845:HLA-DRB4 Chains; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins