An active CD8alpha/pMHCI interaction is required for CD8 single positive thymocyte differentiation.
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.
Kang
Yoon-Joong
YJ
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, USA.
Wang
Xiaosong
X
Lin
Sue-Jane
SJ
Hsu
Yen-Ming
YM
Chang
Hsiu-Ching
HC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; C433839:CD8alphabeta antigen; D015395:Histocompatibility Antigens Class I