Cavani A, Hackett C J, Wilson K J, Rothbard J B, Katz S I
Dermatology Branch, National Institutes of Health, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1995 Feb 1;154(3):1232-8.
Although protein-derived nominal Ags have, in many instances, been precisely determined, the epitopes recognized by hapten-specific CD4+ T cells responsible for contact sensitization have not been defined. To better understand the nature of the precise epitopes generated after hapten interaction with Langerhans cells (LC), we assessed the ability of TNP-modified I-Ak- and I-Au-binding peptides to activate hapten-specific CD4+ T cells obtained respectively from TNCB-primed C3H (H-2k) and PL/j (H-2u) mice. Using LC as APC, I-Ak-restricted TNP-specific CD4+ T cells proliferated in the presence of the synthetic peptide hen egg lysozyme 52-61 derivatized with TNP at position 56, and less so when TNP was coupled at positions 53 or 59. Similarly, I-Au-restricted TNP-specific CD4+ T cells from PL/j mice were triggered by the synthetic I-Au-binding 13 mer poly(A)-Y5-R6 TNP-modified at position 4, and to a limited extent with TNP coupled in positions 7 or 10. Our results indicate that hapten-modified MHC class II binding nonautologous peptides are recognized by hapten-specific CD4+ T cells and that precise positioning of hapten molecules on peptides binding MHC class II molecules is required for optimal CD4+ T cell recognition. These findings provide insight into the manner in which haptens are recognized by T cells involved in contact sensitivity and should facilitate the study and design of specific therapies for the manipulation of hapten-specific CD4+ T cell responses.
尽管在许多情况下，蛋白质衍生的名义抗原已被精确确定，但负责接触致敏的半抗原特异性CD4 + T细胞识别的表位尚未明确。为了更好地理解半抗原与朗格汉斯细胞（LC）相互作用后产生的精确表位的性质，我们评估了TNP修饰的I-Ak和I-Au结合肽激活分别从TNCB致敏的C3H（H-2k）和PL/j（H-2u）小鼠获得的半抗原特异性CD4 + T细胞的能力。以LC作为抗原呈递细胞，I-Ak限制的TNP特异性CD4 + T细胞在56位用TNP衍生的合成肽鸡卵溶菌酶52-61存在下增殖，而当TNP偶联在53或59位时增殖较少。同样，来自PL/j小鼠的I-Au限制的TNP特异性CD4 + T细胞由在4位修饰的合成I-Au结合13聚体poly(A)-Y5-R6 TNP触发，在7或10位偶联TNP时触发程度有限。我们的结果表明，半抗原修饰的MHC II类结合非自体肽被半抗原特异性CD4 + T细胞识别，并且半抗原分子在结合MHC II类分子的肽上的精确定位是最佳CD4 + T细胞识别所必需的。这些发现为参与接触敏感性的T细胞识别半抗原的方式提供了见解，并应有助于研究和设计用于操纵半抗原特异性CD4 + T细胞反应的特异性疗法。
