First Author | Kang YJ | Year | 2010 |
Journal | Eur J Immunol | Volume | 40 |
Issue | 3 | Pages | 836-48 |
PubMed ID | 19950178 | Mgi Jnum | J:157734 |
Mgi Id | MGI:4436828 | Doi | 10.1002/eji.200939663 |
Citation | Kang YJ, et al. (2009) An active CD8alpha/pMHCI interaction is required for CD8 single positive thymocyte differentiation. Eur J Immunol 40(3):836-848 |
abstractText | Recognition of viral antigenic peptides bound to major histocompatibility complex class I molecules (MHCI) by TCR is critical for initiating the responses of CD8(+) T cells that ultimately lead to elimination of virus-infected cells. This antigen recognition is enhanced by the CD8 coreceptor through its interaction with the peptide-MHCI complexes (pMHCI). Mouse CD8alphabeta can form two different complexes with pMHCI via either the CD8alpha- or CD8beta-dominated interaction. To understand the functional significance of these complexes in vivo, we generated Tg mice carrying a variant CD8alphabeta (CD8alpha(m3)beta) capable of forming only the CD8beta-dominated CD8alphabeta/pMHCI complex. These mice show sub-optimal thymic differentiation with reduced populations of CD8(+) single-positive thymocytes. Tg CD8(+) T cells exhibit a compromised developmental capacity when competing with CD8(+) T cells from B6 mice in mixed bone marrow chimera experiments. However, once these CD8(+) T cells have emigrated to the peripheral lymphoid organs, they exhibit normal effector function against viral infection. Our observations indicate that, in addition to the CD8 activity conferred by CD8beta-dominated CD8alphabeta/pMHCI complexes, full thymocyte differentiation requires additional coreceptor activities conferred by CD8alphaalpha and/or CD8alphabeta with CD8alpha-dominated CD8/pMHCI complexes. |