Obata Y, Satta Y, Moriwaki K, Shiroishi T, Hasegawa H, Takahashi T, Takahata N
Laboratory of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6589-93. doi: 10.1073/pnas.91.14.6589.
In contrast to well-studied "classical" class I genes of the major histocompatibility complex (MHC), the biology of nonclassical class I genes remains largely unexamined. The mouse TL genes constitute one of the best defined systems among nonclassical class I genes in the T region of the MHC. To elucidate the function and the evolution of TL genes and their relationship to classical class I genes, seven TL DNA sequences, including one from a Japanese wild mouse, were examined and compared with those of several mouse and human classical class I genes. The TL genes differ from either classical class I genes or pseudogenes in the extent and pattern of nucleotide substitutions. Natural selection appears to have operated so as to preserve the function of TL, which might have been acquired in an early stage of its evolution. In a putative peptide-binding region encoded by TL genes, the rate of nonsynonymous (amino acid replacing) substitution is considerably lower than that of synonymous substitution. This conservation is completely opposite that in classical class I genes, in which the peptide-binding region has evolved to diversify amino acid sequences so as to recognize a variety of antigens. Thus, it is suggested that the function of TL antigens is distinct from that of classical class I antigens and is related to the recognition of a relatively restricted repertoire of antigens and their presentation to T-cell receptors.
与研究充分的主要组织相容性复合体（MHC）的“经典”I类基因相比，非经典I类基因的生物学特性在很大程度上仍未得到研究。小鼠TL基因是MHC T区域非经典I类基因中定义最明确的系统之一。为了阐明TL基因的功能、进化及其与经典I类基因的关系，研究人员检测了包括一只日本野生小鼠的序列在内的7个TL DNA序列，并将其与几个小鼠和人类经典I类基因的序列进行了比较。TL基因在核苷酸替换的程度和模式上与经典I类基因或假基因都不同。自然选择似乎一直在发挥作用以保留TL的功能，这种功能可能在其进化的早期阶段就已获得。在由TL基因编码的一个假定的肽结合区域中，非同义（氨基酸替换）替换率明显低于同义替换率。这种保守性与经典I类基因完全相反，在经典I类基因中，肽结合区域已经进化以使氨基酸序列多样化，从而识别多种抗原。因此，有人提出TL抗原的功能与经典I类抗原不同，并且与识别相对有限的抗原库及其呈递给T细胞受体有关。
