TY - JOUR
T1 - Residues in pockets B and F of HLA-B27 are critical in the presentation of an influenza A virus nucleoprotein peptide and influence the stability of peptide-MHC complexes
AU - Carreno, Beatriz M.
AU - Winter, Christine C.
AU - Taurog, Joel D.
AU - Hansen, Ted H.
AU - Biddison, William E.
N1 - Funding Information:
We wish to thank Drs John Cofigan, Kenneth C. Parker, and Eric Long for reagents, Dr John Gorka for the H3 peptide, Dr Kim Wieties Clary for helpful discussions, Ms Cathy Dimbeck for FACS analysis, and Mr Richard V. Turner for excellent technical assistance. This work was supported in part by NIH grant AI07163 and funds from Monsanto Co.
PY - 1993
Y1 - 1993
N2 - Six pockets, designated A through F, which extend from the peptide binding site of class I HLA molecules, have been postulated to play an important role in determining peptide binding specificity. HLA-B27 mutant molecules with single amino acid substitutions at residues 9his-phe in 24thr←ser, 45glu←thr, and 67cys←ala in pocket B; 114his←asn in pocket D; and 116asp←phe in pocket F have been generated and characterized for their capacity to present an influenza A nucleoprotein peptide (NP 383-391) for cytotoxic T iymphocyte recognition. We report here that substitutions in residues 45, 67, and 116 affect presentation of NP 383-391 when peptide is processed and loaded during viral infection. Using 125l-labeled NP peptide, we demonstrate that substitutions in residues 67 and 116 alter the stability of NP-HLA-B27 complexes. A substitution at position 9 of the NP peptide complements the mutation introduced at residue 116, suggesting that the NP peptide binds with its carboxy terminal amino acid in pocket F. These findings indicate that polymorphic residues within pockets B and F of HLA-B27 play a crucial role in peptide binding and stability of peptide-MHC class I complexes. Furthermore, our results suggest that substitutions at allele-speciflc residues within pockets B and F alter the stability of NP-HLA-B27 complexes resulting in the diminution or abrogation of NP presentation during viral infection.
AB - Six pockets, designated A through F, which extend from the peptide binding site of class I HLA molecules, have been postulated to play an important role in determining peptide binding specificity. HLA-B27 mutant molecules with single amino acid substitutions at residues 9his-phe in 24thr←ser, 45glu←thr, and 67cys←ala in pocket B; 114his←asn in pocket D; and 116asp←phe in pocket F have been generated and characterized for their capacity to present an influenza A nucleoprotein peptide (NP 383-391) for cytotoxic T iymphocyte recognition. We report here that substitutions in residues 45, 67, and 116 affect presentation of NP 383-391 when peptide is processed and loaded during viral infection. Using 125l-labeled NP peptide, we demonstrate that substitutions in residues 67 and 116 alter the stability of NP-HLA-B27 complexes. A substitution at position 9 of the NP peptide complements the mutation introduced at residue 116, suggesting that the NP peptide binds with its carboxy terminal amino acid in pocket F. These findings indicate that polymorphic residues within pockets B and F of HLA-B27 play a crucial role in peptide binding and stability of peptide-MHC class I complexes. Furthermore, our results suggest that substitutions at allele-speciflc residues within pockets B and F alter the stability of NP-HLA-B27 complexes resulting in the diminution or abrogation of NP presentation during viral infection.
KW - Antigen presentation
KW - HLA-B27
KW - MHC class I
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U2 - 10.1093/intimm/5.4.353
DO - 10.1093/intimm/5.4.353
M3 - Article
C2 - 8494822
AN - SCOPUS:0027311958
SN - 0953-8178
VL - 5
SP - 353
EP - 360
JO - International Immunology
JF - International Immunology
IS - 4
ER -