MECHANISMS OF CD8-BETA-MEDIATED T-CELL RESPONSE ENHANCEMENT - INTERACTION WITH MHC CLASS-I BETA(2)-MICROGLOBULIN AND FUNCTIONAL COUPLING TOTCR CD3/

CD8 beta expression results in enhanced IL-2 production and/or altered specificity in allogeneic MHC class I-restricted T cell hybridomas. E xpression of chimeric CD8 beta-alpha molecules (extracellular CD8 beta , transmembrane and cytoplasmic CD8 alpha) also results in enhancement of T hybridoma responses to alloantigen, suggesting that at least par t of CD8 beta's ability to influence responses similar to those of mat ure CD8(+) T cells is mediated by its extracellular domain. Current da ta suggest that CD8 beta-mediated response enhancement proceeds throug h mechanisms similar to those mediated by CD8 alpha, i.e., interacting with MHC class I and stabilizing CD8-associated Lck activity. In this study we present evidence that the extracellular portion of CD8 beta is capable of independent interaction with MHC class I/beta(2)m dimers in the absence of CD8 alpha. In addition, CD8 beta may enhance intera ction with MHC class I/beta(2)m when associated with CD8 alpha. We als o present evidence from T hybridoma responses suggesting that the extr a- cellular portion of CD8 beta is uniquely capable of efficient inter action with the TCR/CD3 complex and may couple the TCR/CD3 complex to other surface components capable of enhancing TCR-mediated signals. Th is represents the first evidence that a critical coreceptor function c an be preferentially associated with the CD8 beta subunit.