Homogenization of TCR repertoires within secondary CD62L high and CD62L low virus-specific CD8 + T cell populations

Abstract

Influenza virus-specific CD8 + T cell clonotypes generated and maintained in C57BL/6J mice after respiratory challenge were found previously to distribute unequally between the CD62L low "effector" (T EM) and CD62L high "central" (T CM) memory subsets. Defined by the CDR3β sequence, most of the prominent TCRs were represented in both the CD62L high and CD62LM low subsets, but there was also a substantial number of diverse, but generally small, CD62L high-onIy clonotypes. The question asked here is how-secondary challenge influences both the diversity and the continuity of TCR representation in the T CM and T EM subsets generated following primary exposure. The experiments use single-cell RT-PCR to correlate clonotypic composition with CD62L phenotype for secondary influenza-specific CD8 + T cell responses directed at the prominent D bNP 366 and D bPA 224 epitopes. In both the acute and long-term memory phases of the recall responses to these epitopes, we found evidence of a convergence of TCR repertoire expression for the CD62L low and CD62L high populations. In fact, unlike the primary response, there were no significant differences in clonotypic diversity between the CD62L low and CD62L high subsets. This "TCR homogenization" for the CD62L high and CD62L low CD8 + populations recalled after secondary challenge indicates common origin, most likely from the high prevalence populations in the CD62L high central memory set. Our study thus provides key insights into the TCR diversity spectrum for CD62L high and CD62L low T cells generated from a normal, unmanipulated T cell repertoire following secondary challenge. A better understanding of TCR selection and maintenance has implications for improved vaccine and immunotherapy protocols. Copyright © 2008 by The American Association of Immunologists, Inc.