Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size

RM Chicz, RG Urban, WS Lane, JC Gorga, LJ Stern… - Nature, 1992 - nature.com
RM Chicz, RG Urban, WS Lane, JC Gorga, LJ Stern, DAA Vignali, JL Strominger
Nature, 1992nature.com
PEPTIDES bound to class I molecules are 8–10 amino acids long, and possess a binding
motif representative of peptides that bind to a given class I allele1–4. In the only published
study of naturally processed peptides bound to class II molecules (mouse I–Ab and I–Eb),
these peptides were longer (13–17 amino acids) and had heterogenous carboxy terminals
but precise ammo-terminal truncations5. Here we report the characterization of acid-eluted
peptides bound to HLA-DR1 by high-performance liquid chromatography, mass …
Abstract
PEPTIDES bound to class I molecules are 8–10 amino acids long, and possess a binding motif representative of peptides that bind to a given class I allele1–4. In the only published study of naturally processed peptides bound to class II molecules (mouse I–Ab and I–Eb), these peptides were longer (13–17 amino acids) and had heterogenous carboxy terminals but precise ammo-terminal truncations5. Here we report the characterization of acid-eluted peptides bound to HLA-DR1 by high-performance liquid chromatography, mass spectrometry and microsequencing analyses. The relative molecular masses of the peptides varied between 1,602 and 2,996 (13–25 residues), the most abundant individual Mr values being between 1,700 and 1,800, corresponding to an average peptide length of 15 residues. Complete sequence data were obtained for twenty peptides derived from five epitopes, of which all but one were from self proteins. These peptides represented sets nested at both the N- and C-terminal ends. Binding experiments confirmed that all of the isolated peptides had high affinity for the groove of DR1. Alignment of the peptides bound to HLA-DR1 and the sequences of 35 known HLA-DRl-binding peptides revealed a putative motif. Although peptides bound to class II molecules may have some related features (due to the nonpolymorphic HLA-DR α-chain), accounting for degenerate binding to different alleles6, particular amino acids in the HLA-DR β-chains presumably define allelic specificity of peptide binding.
nature.com