Mechanisms of CD8β-Mediated T Cell Response Enhancement: Interaction with MHC Class I/β2-Microglobulin and Functional Coupling to TCR/CD3

Abstract

Abstract CD8β expression results in enhanced IL-2 production and/or altered specificity in allogeneic MHC class I-restricted T cell hybridomas. Expression of chimeric CD8β-α molecules (extracellular CD8β, transmembrane and cytoplasmic CD8α) also results in enhancement of T hybridoma responses to alloantigen, suggesting that at least part of CD8β’s ability to influence responses similar to those of mature CD8+ T cells is mediated by its extracellular domain. Current data suggest that CD8β-mediated response enhancement proceeds through mechanisms similar to those mediated by CD8α, i.e., interacting with MHC class I and stabilizing CD8-associated Lck activity. In this study we present evidence that the extracellular portion of CD8β is capable of independent interaction with MHC class I/β2m dimers in the absence of CD8α. In addition, CD8β may enhance interaction with MHC class I/β2m when associated with CD8α. We also present evidence from T hybridoma responses suggesting that the extracellular portion of CD8β is uniquely capable of efficient interaction with the TCR/CD3 complex and may couple the TCR/CD3 complex to other surface components capable of enhancing TCR-mediated signals. This represents the first evidence that a critical coreceptor function can be preferentially associated with the CD8β subunit.