Mechanisms of CD8beta-mediated T cell response enhancement: interaction with MHC class I/beta2-microglobulin and functional coupling to TCR/CD3.
CD8beta expression results in enhanced IL-2 production and/or altered specificity in allogeneic MHC class I-restricted T cell hybridomas. Expression of chimeric CD8beta-alpha molecules (extracellular CD8beta, transmembrane and cytoplasmic CD8alpha) also results in enhancement of T hybridoma responses to alloantigen, suggesting that at least part of CD8beta's ability to influence responses similar to those of mature CD8+ T cells is mediated by its extracellular domain. Current data suggest that CD8beta-mediated response enhancement proceeds through mechanisms similar to those mediated by CD8alpha, i.e., interacting with MHC class I and stabilizing CD8-associated Lck activity. In this study we present evidence that the extracellular portion of CD8beta is capable of independent interaction with MHC class I/beta2m dimers in the absence of CD8alpha. In addition, CD8beta may enhance interaction with MHC class I/beta2m when associated with CD8alpha. We also present evidence from T hybridoma responses suggesting that the extracellular portion of CD8beta 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 CD8beta subunit.
Wheeler
C J
CJ
Department of Medicine, Stanford University Medical Center, CA 94305, USA.
Chen
J Y
JY
Potter
T A
TA
Parnes
J R
JR
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006825:Hybridomas; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011940:Receptor Aggregation / Q000276:immunology; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000276:immunology*
D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D001613:beta 2-Microglobulin