An Altered Position of the α2 Helix of MHC Class I Is Revealed by the Crystal Structure of HLA-B*3501

Smith, Kathrine J.; Reid, S. W. J.; Stuart, David I.; McMichael, Andrew J.; Jones, E Y; Bell, John I.

doi:10.1016/s1074-7613(00)80429-x

Cited by 159 publications

(118 citation statements)

References 39 publications

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“…1B). There is close superposition between the TCRaccessible surfaces of the two MHC molecules in all but the short portion of the a2 helix (residues 141-152), a characteristic difference of HLA-B*B35 alleles compared to other pMHC structures as previously noted [11].…”

Section: Resultssupporting

confidence: 74%

The structure of the human allo‐ligand HLA‐B*3501 in complex with a cytochrome p450 peptide: Steric hindrance influences TCR allo‐recognition

Hourigan¹,

Harkiolaki²,

Peterson³

et al. 2006

Eur J Immunol

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Virus‐specific T cell populations have been implicated in allo‐recognition. The subdominant T cell receptor JL12 recognizes both HLA‐B*0801 presenting the Epstein–Barr virus‐derived peptide FLRGRAYGL and also HLA‐B*3501 presenting the cytochrome p450 self peptide KPIVVLHGY. This cross‐reactivity could promote the rejection of HLA‐B*3501‐positive cells in Epstein–Barr virus‐exposed HLA‐B*0801 recipients. LC13, the dominant TCR against the HLA‐B*0801:FLRGRAYGL complex, fails to recognize HLA‐B*3501:KPIVVLHGY. We report the 1.75‐Angstrom resolution crystal structure of the human allo‐ligand HLA‐B*3501:KPIVVLHGY. Similarities between this structure and that of HLA‐B*0801:FLRGRAYGL may facilitate cross‐recognition by JL12. Moreover, the elevated peptide position in HLA‐B*3501:KPIVVLHGY would provide steric hindrance to LC13, preventing it from interacting in the manner in which it interacts with HLA‐B*0801:FLRGRAYGL. These findings are relevant to understanding the basis of T cell cross‐reactivity in allo‐recognition, optimal transplant donor‐recipient matching and developing specific molecular inhibitors of allo‐recognition.

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Section: Resultssupporting

confidence: 74%

The structure of the human allo‐ligand HLA‐B*3501 in complex with a cytochrome p450 peptide: Steric hindrance influences TCR allo‐recognition

Hourigan¹,

Harkiolaki²,

Peterson³

et al. 2006

Eur J Immunol

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“…Interestingly, the B53 epitope (EBNA1 aa 407-415, HPVGEADYF) was actually a 9-mer that lay within the 11-mer B*3501 epitope (EBNA1 aa 407-417, HPVGEADYFEY). The HLA-B53 and -B35 molecules are very closely related alleles that belong to the B5 cross-reactive group, but differ structurally at the F pocket of the peptide binding groove, which interacts with the peptide C terminus (32,33). Although B35 has a strong preference for Tyr residues at this position, the B53 allele can accommodate either Leu, Ile, Val, Phe, or Tyr (24,32,33), explaining why the shorter peptide with a Phe at position 9 can function as a B53 epitope.…”

Section: Discussionmentioning

confidence: 99%

The Importance of Exogenous Antigen in Priming the Human CD8+ T Cell Response: Lessons from the EBV Nuclear Antigen EBNA1

Blake

Haigh

Shaka’a

et al. 2000

The Journal of Immunology

122

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Mouse models suggest that the processing of exogenous Ag by dendritic cells can be important for priming the CD8+ CTL response. To study the situation in humans, we have exploited the CTL response to EBV infection. In this context EBV expresses eight latent proteins, of which EBV-encoded nuclear Ag (EBNA) 3A, 3B, and 3C appear to be immunodominant for CTL responses, whereas another nuclear Ag, EBNA1, which is completely protected from endogenous presentation via the MHC class I pathway, is thought to induce responses rarely, if ever. Here, using EBNA1 peptides and/or EBNA1 protein-loaded dendritic cells as in vitro stimuli, we have identified memory CTL responses to HLA-B*3501, -B7, and -B53-restricted EBNA1 epitopes that can be as strong as those seen in immunodominant epitopes from the “conventionally processed” EBNA3 Ags. Furthermore, we used HLA-peptide tetramers to show that the primary response to one such EBNA1 epitope constituted up to 5% of the CD8+ T cells in infectious mononucleosis blood, the strongest latent Ag-specific response yet detected in this setting. We conclude that exogenous protein represents a significant source of Ag for priming the human CTL response.

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“…Notably, the binding of TSST-1 is also affected by the nature of bound peptide (34). In the crystal structures of HLA-A2 complexed with five different individual peptides and in two HLA-B*3501 single peptide complexes, the P8 side chain (or its equivalent) points upward while the anchor side chain of the C-terminal amino acid, usually P9, is in the F pocket (29,(35)(36)(37). Val, Asp, His, Arg, Ala, and, with the exception of clone DP10.7, Glu all appear to be acceptable P8 side chains, permitting an HLA-Cw7͞ NKIR2 interaction that leads to inhibition, while P8 Lys permits lysis.…”

Section: Discussionmentioning

confidence: 99%

“…The cytolytic activity of NK lines and clones against the various HLA-C transfectants and mutants was assessed in 5-hr 35 S release assays (4 hr for the RMA-S targets) in which effector cells were admixed with 5 ϫ 10 3 [ 35 S]methionine-labeled targets at different effector:target (E:T) ratios in U-bottomed microtiter plates. Assays were terminated by centrifugation at 1,000 rpm for 10 min at 4ЊC, and 100 l of the supernatant was collected for liquid scintillation counting.…”

Section: Methodsmentioning

confidence: 99%

Self and viral peptides can initiate lysis by autologous natural killer cells

Mandelboim

Wilson

Valés‐Gómez

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Natural killer (NK) cells are inhibited by specific allotypes of class I major histocompatibility complex ligands recognized by polymorphic inhibitory receptors (e.g., NKIR1 and NKIR2). NK1-and NK2-specific clones recognize two groups of HLA-C allotypes that are distinguished by a dimorphism at residue 80 in the ␣1 helix (␣Lys-80 and ␣Asn-80, respectively). ''Empty'' HLA-Cw7 expressed in peptide transporter-deficient cells and HLA-Cw7 loaded with several peptides each functioned as inhibitory ligands for NK2 lines and clones. However, loading of HLA-Cw7 with two other peptides derived from glutamic acid decarboxylase or coxsackie virus (each of which has been associated with autoimmune diabetes mellitus) abrogated this inhibitory recognition. Both peptides contained Lys at P8 of the epitope. Substitution of P8 with Ala or two other basic amino acids, His and Arg, resulted in peptides that were inhibitory, as were peptides with P8 Val, Glu, or Asn. The manner in which a Lys at P8 might affect recognition is discussed, together with a hypothesis for a novel mechanism by which an autoimmune disease might be initiated.

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An Altered Position of the α2 Helix of MHC Class I Is Revealed by the Crystal Structure of HLA-B*3501

Cited by 159 publications

References 39 publications

The structure of the human allo‐ligand HLA‐B*3501 in complex with a cytochrome p450 peptide: Steric hindrance influences TCR allo‐recognition

The structure of the human allo‐ligand HLA‐B*3501 in complex with a cytochrome p450 peptide: Steric hindrance influences TCR allo‐recognition

The Importance of Exogenous Antigen in Priming the Human CD8+ T Cell Response: Lessons from the EBV Nuclear Antigen EBNA1

Self and viral peptides can initiate lysis by autologous natural killer cells

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