Analysis of human TCRβ repertoire by a RARE-sequencing method reveals distinct features of TCRβ diversity and distribution and their alterations with age (IRM10P.758)

Abstract The T cell receptor (TCR) repertoire (diversity and distribution) is a vital parameter of the overall function of T cells. Reduction of TCR diversity and alteration of TCR distribution is believed to occur with age and acts as a major contributor for age-associated decline of immune function. However, neither the actual size of the TCR repertoire nor its precise age-related change have been directly determined. Applying a RACE-next generation sequencing (RAP-Seq) method, we assessed the TCRβ repertoire of blood CD4+ and CD8+ T cells of 13 adults (21-94 years old) including 6 adults with longitudinal samples. We found that TCRβ diversity of CD4+ T cells is 3-4 times greater than CD8+ T cells. TCRβ CDR3 was distinct between CD4+ and CD8+ T cells with preferential amino acid usage. Reduced TCRβ diversity and expanded highly abundant TCRβ clones occurred from middle to old subjects (45-75 years old) but not in very old subjects (80-94 years old). Together, these findings reveal the distinct features and actual age-associated changes of TCRβ repertoire, which could serve as a measure of the immune competency and a guide for the clinical intervention in older humans.