Vogel J M, Davis A C, McKinney D M, McMillan M, Martin W J, Goodenow R S
Department of Genetics, University of California, Berkeley 94720.
J Exp Med. 1988 Nov 1;168(5):1781-800. doi: 10.1084/jem.168.5.1781.
The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H-2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides.
C3HfB/HeN（C3Hf）小鼠品系表达一种H-2Kk分子，以前称为H-2Kkv1，其在结构和功能上与亲代C3H品系的H-2Kk不同。通过分子遗传学分析，我们证明C3Hf H-2K基因相对于C3H等位基因携带纯合编码区突变，表明C3Hf符合指定突变单倍型H-2km2的要求。C3Hf H-2Kkm2在第3外显子的14个连续核苷酸内有四个核苷酸的单个簇状取代。由于该序列在C3H和C3Hf的H-2Dk的同源位置也完整存在，H-2Kkm2突变的起源与来自H-2Dk供体基因的非互惠序列转移一致，类似于为产生H-2Kb突变提出的机制。H-2Kkm2突变编码在第95、98和99位的三个簇状氨基酸取代，这些取代位于H-2Kkm2分子肽抗原结合裂隙底部的一条大β链上。这些氨基酸取代的性质和位置相对于任何其他已知的H-2突变体或HLA变体都是独特的，并强调了β折叠片层在影响CTL识别中的重要性。这些结果表明，H-2Kkm2同种抗原性可能很大程度上源于自身细胞肽呈递的改变。
