Sugita M, Moody D B, Jackman R M, Grant E P, Rosat J P, Behar S M, Peters P J, Porcelli S A, Brenner M B
Lymphocyte Biology Section, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Clin Immunol Immunopathol. 1998 Apr;87(1):8-14. doi: 10.1006/clin.1997.4500.
Despite identification of the CD1 family of molecules in the late 1970s, the function of CD1 was undetermined for more than a decade. Recent evidence has established that CD1 molecules comprise a novel lineage of antigen-presenting molecules, distinct from major histocompatibility complex (MHC) class I and class II molecules. Unlike the MHC molecules, which bind short peptides in their antigen-binding groove for presentation to either CD4+ or CD8+ T cells bearing alpha beta T cell receptors, the CD1 molecules appear to accommodate lipid and glycolipid antigens in their hydrophobic cavity for presentation to a wide variety of T cells, including double-negative alpha beta and gamma delta T cells and CD8+ alpha beta T cells. By using a unique cytoplasmic signal, some CD1 molecules traffic to endosomal compartments for sampling mycobacteria-derived lipid antigens, and subsequently lipid antigen-loaded CD1 molecules are expressed on the cell surface to activate specific T cells. These CD1-restricted T cells kill mycobacteria-infected cells and secrete interferon-gamma, indicating a potential role of CD1-mediated T cell responses in clearing mycobacterial infection. The identification of an MHC-independent antigen presentation pathway for nonpeptide antigens provides new insights into immunoregulation and host defense.
尽管在20世纪70年代末就已鉴定出CD1分子家族，但CD1的功能在十多年里一直未明。最近的证据表明，CD1分子构成了一类新型的抗原呈递分子谱系，不同于主要组织相容性复合体（MHC）Ⅰ类和Ⅱ类分子。与在抗原结合槽中结合短肽以呈递给带有αβT细胞受体的CD4⁺或CD8⁺T细胞的MHC分子不同，CD1分子似乎在其疏水腔内容纳脂质和糖脂抗原，以呈递给多种T细胞，包括双阴性αβ和γδT细胞以及CD8⁺αβT细胞。通过利用独特的胞质信号，一些CD1分子转运至内体区室以摄取分枝杆菌衍生的脂质抗原，随后负载脂质抗原的CD1分子在细胞表面表达以激活特定T细胞。这些受CD1限制的T细胞杀死分枝杆菌感染的细胞并分泌γ干扰素，表明CD1介导的T细胞反应在清除分枝杆菌感染中具有潜在作用。非肽抗原的MHC非依赖性抗原呈递途径的鉴定为免疫调节和宿主防御提供了新的见解。
