Schulz M, Aichele P, Schneider R, Hansen T H, Zinkernagel R M, Hengartner H
Department of Experimental Pathology, University Hospital, Zürich, Switzerland.
Eur J Immunol. 1991 May;21(5):1181-5. doi: 10.1002/eji.1830210513.
The primary immune response of cytotoxic T lymphocytes in H-2d and H-2q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major T cell epitope of amino acids 112-132 on the viral nucleoprotein (NP). The molecules responsible for presentation of the T cell epitope NP112-132 are in both haplotypes the MHC class I L antigens (Ld, Lq). Truncations of the amino and carboxy termini of the NP 112-132 sequence revealed the nonapeptide RPQASGVYM (NP118-126) as a most effective peptide antigen, but even the tetrapeptide GVYM was recognized by CTL of both haplotypes in a class I antigen-restricted specificity. When tyrosine (Y) or methionine (M) were substituted with alanine, CTL recognition of the altered nonamer required 10(6) to 10(8) times higher peptide concentrations and in one case (Y----A on Ld) the peptide was not recognized at all. Up-modulation of the expression of Ld and Lq class I antigens as measured by flow cytometry correlated with the ability to present the peptide antigens. The only exception was peptide NP118-126 (M----A), which was recognized by T cells on L-Ld and L-Lq target cells but failed to up-regulate Ld and Lq antigens.
H-2d和H-2q小鼠中细胞毒性T淋巴细胞对淋巴细胞性脉络丛脑膜炎病毒感染的主要免疫反应主要针对病毒核蛋白（NP）上氨基酸112 - 132的常见主要T细胞表位。在这两种单倍型中，负责呈递T细胞表位NP112 - 132的分子是MHC I类L抗原（Ld、Lq）。NP 112 - 132序列的氨基和羧基末端截短后，发现九肽RPQASGVYM（NP118 - 126）是最有效的肽抗原，但即使是四肽GVYM也能被两种单倍型的CTL以I类抗原限制性特异性识别。当酪氨酸（Y）或甲硫氨酸（M）被丙氨酸取代时，CTL对改变后的九肽的识别需要高10^6到10^8倍的肽浓度，并且在一种情况下（Ld上的Y→A），该肽根本不被识别。通过流式细胞术测量的Ld和Lq I类抗原表达的上调与呈递肽抗原的能力相关。唯一的例外是肽NP118 - 126（M→A），它能被L - Ld和L - Lq靶细胞上的T细胞识别，但未能上调Ld和Lq抗原。
