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can affect MHC-I binding peptide length preferences, but the mechanism remains unclear. Using a random peptide library combined with LC-MS/MS and <i>de novo</i> sequencing (RPLD-MS) technique, we found that two swine MHC-I molecules with high sequence homology, SLA-1*04:01 and SLA-1*13:01, had significant differences in length preference of the binding peptides. Compared with SLA-1*04:01, SLA-1*13:01 binds fewer short peptides with 8-10 amino acids, but more long peptides. A dodecapeptide peptide (RW12) can bind to both SLA-1*04:01 and SLA-1*13:01, but their crystal structures indicate that the binding modes are significantly different: the entirety of RW12 is embedded in the peptide binding groove of SLA-1*04:01, but it obviously protrudes from the peptide binding groove of SLA-1*13:01. The structural comparative analysis showed that only five differential amino acids of SLA-1*13:01 and SLA-1*04:01 were involved in the binding of RW12, and they determine the different ways of long peptides binding, which makes SLA-1*04:01 more restrictive on long peptides than SLA-1*13:01, and thus binds fewer long peptides. In addition, we found that the N terminus of RW12 extends from the groove of SLA-1*13:01, which is similar to the case previously found in SLA-1*04:01. However, this unusual peptide binding does not affect their preferences of binding peptide length. Our study will be helpful to understand the effect of polymorphisms on the length distribution of MHC-I binding peptides, and to screen SLA-I-restricted epitopes of different lengths and to design effective epitope vaccines.","bibjson":{"author":[{"initials":null,"lastname":null,"name":"Wei, X.H."},{"initials":null,"lastname":null,"name":"Wang, S."},{"initials":null,"lastname":null,"name":"Zhang, N.Z."},{"initials":null,"lastname":null,"name":"Xia, C."}],"identifier":[{"id":"10.3389/fimmu.2022.820881","type":"doi"}],"issue":[null],"journal":{"iso_abbreviation":null,"name":""},"pages":["-"],"title":"Peptidomes and Structures Illustrate How SLA-I Micropolymorphism Influences the Preference of Binding Peptide Length.","type":"article","url":"https://www.frontiersin.org/articles/10.3389/fimmu.2022.820881/full","volume":[null],"year":[2022]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.50","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6lf9"},"rcsb":{"url":"https://www.rcsb.org/structure/6lf9"}},"species":{"common_name":"Feral Pig","match_type":"histo:assign_species","scientific_name":"Sus scrofa","slug":"sus_scrofa"},"tcr":null,"title":"SLA-1*13:01 binding \"RVEDVTNTAEYW\" at 2.50&#8491; resolution","unique_chain_count":3}}
