Mycobacterium tuberculosis peptide E7/HLA-DRB1 tetramers with different HLA-DR alleles bound CD4 T cells might share identical CDR3 region.

Human CD4 T cells play an important role in the immune response to Mycobacterium tuberculosis (MTB). However, little is known about the spectratyping characteristics of the CD4 T-cell receptor (TCR) α- and β-chains CDR3 region in tuberculosis (TB) patients. We sorted MTB peptide E7-bound CD4 T cells by using E7/HLA-DR tetramers constructed with different HLA-DRB1 alleles and extracted the CDR3 amino-acid sequences of TCR α- and β-chains. The results showed that the CDR3 sequences of E7-bound CD4 T cells were completely or partially identical in a single patient. The sequences of MTB peptide C5-bound CD4 T cells shared another, and non-peptide bound CD4 T cells, as well as unbound CD4 T cells with tetramers were different from each other. Specifically, diverse CDR3 sequences of E7-bound CD4 T cells displayed similar protein tertiary structure in one TB patient. In summary, the TCR α- and β-chains of CDR3 lineage of CD4 T cells in TB patients apparently drifted, and the predominant CDR3 sequences of TCR α- and β-chains that recognized the MTB antigen exhibited peptide specificity, and certain HLA-DR restriction was also established. This study elucidates the possible causes and mechanisms of peptide-specific CD4 T-cell-related presentation against MTB.