CD4+ and CD8+ T cell β antigen receptors have different and predictable V and J gene usage and CDR3 lengths (115.10)

Abstract

Abstract CD8+ and CD4+ T lymphocytes have different and complimentary roles: CD8+ (cytotoxic) T cells directly kill cells presenting non-self epitopes while CD4+ (helper) T cells regulate the immune response to a particular antigen. These T cells recognize antigens by binding to epitope MHC protein complexes, with CD8+ T cells binding class I and CD4+ T cells binding class II MHC protein complexes. While it’s known that the CD8 and CD4 proteins determine which MHC class the T cells bind, it is unknown if the antigen receptor sequences vary between the two populations. The diversity of possible receptors is huge and until recently this diversity precluded the possibility of capturing the antigen receptor repertoire. Adaptive Biotechnologies has developed a novel method that amplifies rearranged T cell receptor β (TCRB) CDR3 sequences and uses high throughput sequencing to sequence millions of TCRB CDR3 chains. To determine if the two populations of T cells have unique TCRB profiles, PBMC from 19 unrelated individuals were sorted 4 ways into CD4+ and CD8+ naïve and memory T cells. V and J gene usage and CDR3 sequence length could distinguish the TCRB CDR3 sequences amplified from CD4+ and CD8+ T cells. These sequence differences can be exploited and used to estimate the proportion of CD4+ to CD8+ T cells in a mixed population of T cells. These data indicate a biological difference between the antigen receptors that bind class I versus class II MHC protein complexes.