UMR 1163, INRA de Biotechnologie des Champignons Filamenteux, IFR86-BAIM. Universités de Provence et de la Méditerranée, ESIL, Marseille Cedex 09, France.
Eur J Immunol. 2010 Oct;40(10):2682-5. doi: 10.1002/eji.201040856.
Understanding the nature of MHC class I presentation preferences is a challenging prospect. Large sets of peptide-MHC-class I complexes have been screened for their binding affinities and recent studies have shown that HLA-A share a preference for binding peptides derived from pathogens; however, no mechanism explaining the observed preferences has been demonstrated so far. In this issue of the European Journal of Immunology, a study demonstrates that HLA-A, but not HLA-B, preferentially recognises peptides enriched in amino acids encoded by sequences with low G+C content, and therefore recognises peptides associated with pathogens - low G+C content being a general feature of lower organisms. The authors of the study provide exciting results contributing to the understanding of the nature of MHC-I presentation preferences and MHC-I evolution. Although significant results are presented by the authors, here, we challenge the interpretation whereby HLA-A has been evolutionarily selected for such a function and appeal for the use of comparative phylogenetic methods to substantiate it. We propose a method to ascertain whether ancestral MHC recognised peptides from pathogens and hence was involved in the non-specific recognition of such organisms. Moreover, we suggest that ancestral MHC may have been involved in innate immune responses before being recruited for adaptive immunity.
理解 MHC I 类呈递偏好的本质是一个具有挑战性的前景。已经筛选了大量的肽-MHC-I 复合物，以检测它们的结合亲和力，最近的研究表明 HLA-A 类分子优先结合来自病原体的肽；然而，到目前为止，还没有证明解释观察到的偏好的机制。在本期《欧洲免疫学杂志》上，一项研究表明 HLA-A 类分子而不是 HLA-B 类分子优先识别富含低 G+C 含量序列编码氨基酸的肽，因此识别与病原体相关的肽 - 低 G+C 含量是低等生物的一般特征。该研究的作者提供了令人兴奋的结果，有助于理解 MHC-I 类呈递偏好和 MHC-I 类进化的本质。尽管作者提出了重要的结果，但在这里，我们质疑 HLA-A 类分子是为这种功能而进化选择的解释，并呼吁使用比较系统发育方法来证实这一解释。我们提出了一种方法来确定祖先 MHC 是否识别来自病原体的肽，从而参与对这些生物体的非特异性识别。此外，我们认为，祖先 MHC 可能在被招募用于适应性免疫之前就参与了先天免疫反应。
