Idiosyncratic alterations of TCR size distributions affecting both CD4 and CD8 T cell subsets in aging mice

We have used a spectratyping method, which displays the size distribution for the complementarity-determining region 3 (CDR3) for T cells utilizing a specific TCR-Vbeta gene, to examine the effects of aging on the TCR repertoire of (BALB/c x C57BL/6)F1 hybrid mice. Although the size distributions from T cells of 8-month-old mice were typically symmetrically shaped around one or two bands of intermediate size, spectratypes from mice 16 or 24 months of age were frequently distorted, with specific size classes either over- or underrepresented compared to normal young controls. Each of 12 mice tested at 16 or 24 months of age had a skewed spectratype for at least one of the 24 Vbeta families examined, and some mice had more than 50% of their spectratypes skewed significantly, as judged by a chi2 test. Comparable age-associated skewing of the T cell repertoire occurred in the CD4 and CD8 subsets, and every mouse over 16 months of age exhibited at least one skewed Vbeta family in both the CD4 and CD8 populations. Although the mice were genetically identical and raised in common facilities, their spectratype patterns were nonetheless idiosyncratic: i.e., the specific set of abnormalities was distinct for each individual old mouse. Whether these distortions of the TCR repertoire in middle-aged and older mice lead to alterations in immune function remains to be determined.