Antigen specific changes of CDR3 fragment distribution of Vδ2 chain of human γδ T cells stimulated by Mycobacterium tuberculosis heat resistant antigen (70.11)

Abstract

Abstract Recent studies show that phosphate antigen activated γδ T cells fail to, but Mycobacterium tuberculosis (Mtb) activated γδ T cells potentially inhibit intracellular Mtb growth, and BCG-stimulated γδ T cells display more restricted TCR diversity than phosphate activated γδ T cells. Mtb heat resistant antigen (Mtb-HAg), peptide antigen, has been shown to preferentially stimulate Vγ9Vδ2 T cells. However, the characteristics of diversity of TCR Vδ2 region of Mtb-HAg stimulated Vγ9Vδ2 T cells has not been investigated. In this study, by using size-spectratyping analysis of length of complementarity-determining region (CDR) 3 fragment of Vδ2 gene, the length of the predominant peaks of CDR3 fragment of Vδ2 gene in γδ T cells that stimulated by Mtb-HAg was significantly larger than that in γδ T cells cultured with IL-2 only and that in fresh PBMC groups. However, there were no significant different changes in the variations and length of CDR3 fragment of all other subfamilies of V gene of γδ T cells stimulated with Mtb-HAg. By sequencing Vδ2-CDR3 transfected clones, Vδ2-CDR3 regions showed two conserved “CACD” and “FGXG” at the N-terminus and the C-terminus, respectively. In conclusion, our results indicate that biased distribution of CDR3 fragment of Vγ9Vδ2+ T cells stimulated by Mtb-HAg is antigen specific changed and the clonally restricted. There might be important implications for the development of prophylactic vaccines related to protective and pathogen-specific γδ T cells.