Moody D B, Reinhold B B, Reinhold V N, Besra G S, Porcelli S A
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston MA 02115, USA.
Immunol Lett. 1999 Jan;65(1-2):85-91. doi: 10.1016/s0165-2478(98)00129-1.
Antigen presenting cells (APCs) expressing CD1b mediate the specific T cell recognition of mycobacterial lipid antigens. These lipid antigens require internalization by APCs prior to presentation, but the detailed mechanisms of uptake and intracellular processing are not known. Here we have examined several steps in the presentation of two related classes of CD1b-presented antigens, free and glycosylated mycolates. T cell recognition of glucose monomycolate (GMM) was blocked by agents that fix APC membranes or neutralize the pH of endosomes, indicating a requirement for GMM uptake into an acidic compartment prior to recognition. Different T cell lines responded to free mycolate or GMM without crossreactivity, yet both antigens were taken up by APCs at the same rate. This demonstrated that differential recognition of these antigens resulted from T cell specificity for their hydrophilic caps and that APCs were unable to interconvert these antigens by enzymatic or chemical deglycosylation or glycosylation. APCs were also unable to cleave mycobacterial trehalose dimycolate (TDM) at its most chemically labile linkages to yield antigenic free mycolates or GMM. Our results indicate that these mycolate-containing antigens are resistant to chemical or enzymatic cleavage by APCs, suggesting that molecular trimming is not a universal feature of lipid antigen processing.
表达CD1b的抗原呈递细胞（APC）介导对分枝杆菌脂质抗原的特异性T细胞识别。这些脂质抗原在呈递之前需要被APC内化，但摄取和细胞内加工的详细机制尚不清楚。在这里，我们研究了两类相关的由CD1b呈递的抗原（游离和糖基化的霉菌酸）呈递过程中的几个步骤。单霉菌酸葡萄糖酯（GMM）的T细胞识别被固定APC膜或中和内体pH值的试剂所阻断，这表明在识别之前GMM需要摄取到酸性区室中。不同的T细胞系对游离霉菌酸或GMM有反应且无交叉反应，但两种抗原被APC摄取的速率相同。这表明这些抗原的差异识别是由于T细胞对其亲水性帽的特异性，并且APC无法通过酶促或化学去糖基化或糖基化作用将这些抗原相互转化。APC也无法在其化学上最不稳定的连接点切割分枝杆菌海藻糖二霉菌酸酯（TDM）以产生抗原性游离霉菌酸或GMM。我们的结果表明，这些含霉菌酸的抗原对APC的化学或酶促切割具有抗性，这表明分子修剪不是脂质抗原加工的普遍特征。
