Novak Z, Boyer M, Kilgannon P, Fraga E, Fotedar A, Singh B
Department of Immunology, University of Alberta, Edmonton, Canada.
Cell Immunol. 1992 Mar;140(1):206-18. doi: 10.1016/0008-8749(92)90188-u.
The immune system utilizes a diverse T cell repertoire for the recognition of foreign antigens in the context of self MHC gene products. We have examined the potential diversity of the T cell response directed to a immunodominant repeating tripeptide epitope (EYA)5. This peptide represents one of the two T cell epitopes on the synthetic alpha-helical polypeptide antigen Poly 18, Poly EYK(EYA)5 in H-2d mice and does not require antigen processing prior to presentation to Poly 18-specific T cell hybridomas. The T cell response directed to the repeating tripeptide epitope (EYA)5 is extremely heterogenous even though the epitope has a relatively simple amino acid sequence. We have analyzed the fine specificity of 21 randomly chosen Poly 18-reactive, (EYA)5-specific and H-2d-restricted T cell hybridomas derived from H-2d, H-2bxd, and H-2b----H-2bxd Poly 18-responding mice to determine the number of unique antigen reactivity patterns represented by this T cell population. We used alanine- and/or lysine-substituted (EYA)5 peptides and a panel of haplotype-varied splenocytes and observed a great deal of microheterogeneity in response. We find that 13 of the 21 hybridomas have a distinct fine antigen specificity and T cell receptors. The binding of (EYA)5 to the antigen-binding groove of I-Ad appears to generate a highly diversified T cell response. Therefore, (EYA)5-I-Ad complex allows the activation of unrelated T cell clonotypes with the same overall antigen specificity and MHC restriction, but with distinct microheterogeneity in response and receptor usage.
免疫系统利用多样化的T细胞库在自身MHC基因产物的背景下识别外来抗原。我们已经研究了针对免疫显性重复三肽表位(EYA)5的T细胞反应的潜在多样性。该肽是合成的α-螺旋多肽抗原Poly 18、H-2d小鼠中的Poly EYK(EYA)5上的两个T细胞表位之一，在呈递给Poly 18特异性T细胞杂交瘤之前不需要抗原加工。尽管该表位的氨基酸序列相对简单，但针对重复三肽表位(EYA)5的T细胞反应却极其异质。我们分析了21个随机选择的来自H-2d、H-2bxd和H-2b----H-2bxd Poly 18反应小鼠的Poly 18反应性、(EYA)5特异性和H-2d限制性T细胞杂交瘤的精细特异性，以确定该T细胞群体所代表的独特抗原反应模式的数量。我们使用丙氨酸和/或赖氨酸取代的(EYA)5肽以及一组单倍型不同的脾细胞，并观察到大量的反应微异质性。我们发现21个杂交瘤中有13个具有独特的精细抗原特异性和T细胞受体。(EYA)5与I-Ad抗原结合槽的结合似乎产生了高度多样化的T细胞反应。因此，(EYA)5-I-Ad复合物允许激活具有相同总体抗原特异性和MHC限制性但反应和受体使用具有明显微异质性的不相关T细胞克隆型。
