scholarly journals Efficient Generation of Major Histocompatibility Complex Class I-Peptide Complexes Using Synthetic Peptide Libraries

1998 ◽  
Vol 273 (5) ◽  
pp. 2874-2884 ◽  
Author(s):  
James Stevens ◽  
Karl-Heinz Wiesmüller ◽  
Patrick J. Barker ◽  
Peter Walden ◽  
Geoffrey W. Butcher ◽  
...  
1993 ◽  
Vol 177 (6) ◽  
pp. 1713-1721 ◽  
Author(s):  
E M Rohren ◽  
L R Pease ◽  
H L Ploegh ◽  
T N Schumacher

The set of peptides that is bound by a given major histocompatibility complex class I product can be described by one or two properly spaced anchor residues, and two properly spaced peptide termini, approximately 8-10 residues apart. Using radiolabeled peptide libraries, we examined whether mutations in those "pockets" in class I Kb molecules that do not seem critically involved in the interaction with the peptide anchor residues, do exert an effect on the set of preferred peptides. We find that mutations in all the pockets found in the structure of Kb have a significant effect on the peptide preference of the molecule, and their recognition by cytotoxic T cells. Alterations in substrate specificity are also observed for mutations involving residues that interact with main chain atoms in both peptide termini. These findings challenge a static view of the interaction of peptide termini with their respective pockets in the class I molecule, and imply a role for the minor pockets in peptide selectivity.


2021 ◽  
Vol 12 ◽  
Author(s):  
Patricia T. Illing ◽  
Andy van Hateren ◽  
Rachel Darley ◽  
Nathan P. Croft ◽  
Nicole A. Mifsud ◽  
...  

Abacavir hypersensitivity syndrome can occur in individuals expressing the HLA-B*57:01 major histocompatibility complex class I allotype when utilising the drug abacavir as a part of their anti-retroviral regimen. The drug is known to bind within the HLA-B*57:01 antigen binding cleft, leading to the selection of novel self-peptide ligands, thus provoking life-threatening immune responses. However, the sub-cellular location of abacavir binding and the mechanics of altered peptide selection are not well understood. Here, we probed the impact of abacavir on the assembly of HLA-B*57:01 peptide complexes. We show that whilst abacavir had minimal impact on the maturation or average stability of HLA-B*57:01 molecules, abacavir was able to differentially enhance the formation, selectively decrease the dissociation, and alter tapasin loading dependency of certain HLA-B*57:01-peptide complexes. Our data reveals a spectrum of abacavir mediated effects on the immunopeptidome which reconciles the heterogeneous functional T cell data reported in the literature.


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