Moody D Branch
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Adv Immunol. 2006;89:87-139. doi: 10.1016/S0065-2776(05)89003-0.
CD1 proteins have been conserved throughout mammalian evolution and function to present lipid antigens to T cells. Crystal structures of CD1-lipid complexes show that CD1 antigen-binding grooves are composed of four pockets and two antigen entry portals. This structural information now provides a detailed understanding of how CD1-binding grooves capture a surprisingly diverse array of lipid ligands. CD1-expressing APCs are able to acquire lipid antigens from their own pool of lipids and from exogenous sources, including microbial pathogens, bystander cells, or even the systemic circulation. CD1 proteins bind to certain antigens using high stringency loading reactions within endosomes that involve low pH, glycosidases, and lipid transfer proteins. Other antigens can directly load onto CD1 proteins using low stringency mechanisms that are independent of cellular factors. New evidence from in vivo systems shows that CD1-restricted T cells influence outcomes in infectious, autoimmune, and allergic diseases. These studies lead to a broader view of the natural function of alphabeta T cells, which involves recognition of both cellular proteins and lipids.
CD1蛋白在整个哺乳动物进化过程中一直保守，并发挥着将脂质抗原呈递给T细胞的功能。CD1-脂质复合物的晶体结构表明，CD1抗原结合凹槽由四个口袋和两个抗原进入通道组成。这一结构信息现在为理解CD1结合凹槽如何捕获惊人多样的脂质配体提供了详细的认识。表达CD1的抗原呈递细胞能够从自身的脂质库以及包括微生物病原体、旁观者细胞甚至全身循环等外源性来源获取脂质抗原。CD1蛋白利用内体中涉及低pH值、糖苷酶和脂质转运蛋白的高严格性装载反应与某些抗原结合。其他抗原可以使用独立于细胞因子的低严格性机制直接装载到CD1蛋白上。来自体内系统的新证据表明，CD1限制性T细胞会影响感染性、自身免疫性和过敏性疾病的结局。这些研究使人们对αβT细胞的自然功能有了更广泛的认识，其涉及对细胞蛋白和脂质的识别。
