van Ham S M, Grüneberg U, Malcherek G, Bröker I, Melms A, Trowsdale J
Human Immunogenetics Laboratory, Imperial Cancer Research Fund, Holborn, London, United Kingdom.
J Exp Med. 1996 Nov 1;184(5):2019-24. doi: 10.1084/jem.184.5.2019.
Human histocompatibility leukocyte antigen (HLA)-DM is a facilitator of antigen presentation via major histocompatibility complex (MHC) class II molecules. In the absence of HLA-DM, MHC class II molecules do not present natural peptides, but tend to remain associated with class II-associated invariant chain peptides (CLIP). Recently, DM was shown to catalyze the release of CLIP from HLA-DR. We have investigated which peptides bound to HLA-DR are vulnerable to release upon encountering DM. By directed substitution of allele-specific anchor residues between CLIP and DR3-cognate peptides and the application of recombinant DM we show that DM catalyzes the release of those peptides bound to HLA-DR3 that do not have appropriate anchor residues and, hence, no optimal ligand binding motif. Thus, HLA-DM acts as a peptide editor, facilitating selection of peptides that stably bind to class II molecules for eventual presentation to the immune system from the pool of available peptides.
人类组织相容性白细胞抗原（HLA）-DM是通过主要组织相容性复合体（MHC）II类分子进行抗原呈递的促进因子。在缺乏HLA-DM的情况下，MHC II类分子不呈递天然肽段，而是倾向于与II类相关恒定链肽段（CLIP）保持结合。最近，已证明DM可催化CLIP从HLA-DR上释放。我们研究了哪些与HLA-DR结合的肽段在遇到DM时容易被释放。通过在CLIP和DR3同源肽段之间定向取代等位基因特异性锚定残基，并应用重组DM，我们发现DM催化从HLA-DR3上释放那些没有合适锚定残基、因此也没有最佳配体结合基序的肽段。因此，HLA-DM充当肽段编辑器，促进从可用肽段库中选择能稳定结合II类分子并最终呈递给免疫系统的肽段。
