A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2

Salter, Russell D.; Benjamin, Richard J.; Wesley, Pamela K.; Buxton, Sarah E.; Garrett, T.P.J.; Clayberger, Carol; Krensky, Alan M.; Norment, Anne M.; Littman, Dan R.; Parham, Peter

doi:10.1038/345041a0

Cited by 490 publications

(277 citation statements)

References 48 publications

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“…2c). This finding is similar to that reported by Salter et al, 5 , who noted that T-cell recognition of a3 mutant class I molecules is particularly sensitive to anti-CD8 blocking. Secondary C3H anti-L Q3 CTL recognize both L d and L Q3 and these responses are resistant to blocking by anti-CD8 (Fig.…”

supporting

confidence: 92%

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

Aldrich

Hammer

Jones-Youngblood

et al. 1991

Nature

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As with studies on the Na + / K + pump24, early results on Na+ /Ca 2 + exchange appeared inconsistent with consecutive ion exchange models (see ref. 5 for review). Our work provides strong support for a consecutive Na +/Ca2+ exchange mechanism a nd should facilitate structure-function studies ofthe cloned Na+ /Ca2+ exchanger. The results of both ion jump experiments and steady-state I ~aCa measurements are inconsistent with Ca2+ translocation involving net negative cha rge movement 8• We conclude from our site-density estimates and I NaCa measurements that max imum exchanger turnover rates are about 5,000 S -I . As alread y proposed for the Na + / K + pumpl 2-17 and rod out er segment Na + / Ca2+ , K + excha nger 2 ,22, voltage-dependence must reside in the binding and release of extracellular Na+ or a closely associated occlusion/ deocclusion reaction. THE al and a2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-ce)) repertoire l -3 , Although the a3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CD8 (refs 4, 5). CD8 is important in the selection of T cells as anti-CD8 antibody injected into perinatal mice interfers with this process 6 • We previously used a hybrid class I molecule with the a 11 a2 domains from L d and the a3 domain from Q7 b and showed that this molecule 718 binds an Ld-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes 7• Expression of this molecule in transgenic mice faUs to negatively select a subpopulation of anti-L d cytotoxic T Iymphocytes. In addition, positive selection of virus-specific L d -restricted cytotoxic T lymphocytes does not occur. We conclude that besides the a1la2 domains of class I, the a3 domain plays an important part in both positive and negative selection of antigen-specific cells.To examine the role of the a3 domain of class I molecules in the responses of alloreactive and antigen-specific cytotoxic T Iymphocytes (CTL), we generated two transgenic mouse strains, C3H.L d and C3H.L Q 3, derived from C3H/ HeJ (H_2 k ) mi ce. C3H .L d express inta ct L d , whereas C3H.LQ3 ex press a n LU molecule whose a3 domain is switched with Q7 b . The Q7 b a 3 domain differs from LU at live residues and in addition has a unique three-amino-acid insert at positions 275-277 (ref. 8). We showed that this molecule (L Q3) binds the same viral peptide as L d but is not recognized by peptide-specific CD8-dependent CTL (ref. 7). Similar observations have been reported with a 3 mutant class I molecules not recognized by CD8-dependent CTL, the defect being due to an alteration in the binding site for C D8 (refs 4,5). 80th L d and L Q3 genes contain the same Qj .0

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supporting

confidence: 92%

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

Aldrich

Hammer

Jones-Youngblood

et al. 1991

Nature

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“…Both the CD8 ␣-and ␤-chains are composed of a single extracellular Ig superfamily (IgSF) 3 variable (V) domain, a membrane-proximal hinge (H) region, a transmembrane domain (TM), and a cytoplasmic tail (CY). Biochemical and structural studies have shown that the Ig V domain of CD8␣, in conjunction with that of CD8␤, interacts with MHC class I molecules, thereby allowing the CD8 molecule to function as a coreceptor of the T cell Ag receptor (2)(3)(4)(5)(6)(7).…”

mentioning

confidence: 99%

Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes

Liaw

Chen

Huang

et al. 2007

The Journal of Immunology

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The genomic organization of the chicken CD8α gene was investigated to determine the basis of its polymorphism. Contiguous to the CD8α gene we identified multiple DNA blocks possessing sequences homologous to CD8α. Gene conversions and recombination over evolutionary time among CD8α and these CD8α homologous genes seem to account for the observed polymorphism. Furthermore, these CD8α-like DNAs encode a distinct multigene family of immunoreceptors that have a charged or polar residue in place of the interspecies-conserved CD8α transmembrane proline residue and a short cytoplasmic tail nonhomologous to CD8α. The identification of this novel multigene family with an organization reminiscent of human killer Ig-like receptors raises compelling questions on their evolutionary relationship among immunoreceptors.

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“…In this consideration, the accessibility for human CD8 coreceptors and the SLA molecules on donor endothelium of blood vessel cannot be neglected [20]. The key residues on SLA class I molecule is located in a3 domain, a segment with no polymorphism [21]. To compare the critical sequences of the a3 domain in human (HLA-A * 0201) and in the Chinese pig stains, six amino acid residues from 223 to 228 were checked.…”

Section: The Human Kir-recognized Ligand Sequences In the Class I Molmentioning

confidence: 99%

Novel SLA class I alleles of Chinese pig strains and their significance in xenotransplantation

Chen

Tang

et al. 2003

Cell Res

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To lay background for studying rejection mechanisms in xenotransplantation and developing the strategies for intervention, class I genes of swine leukocyte antigens (SLA) of three Chinese pig strains Bm, Gz and Yn were cloned and sequenced. The cDNA of the class I loci P1 and P14 were amplified by RT-PCR and subjected to insert into sequencing vectors. All six allelic sequences we examined, each two for one Chinese strain, are not identical to those reported, which allows these novel sequences receiving their accession numbers AY102467-AY102472 from GenBank. This study further reveals that the homologies of MHC class I genes in their primary structures and the deduced amino acids between Chinese pigs (SLA) and human (HLA-A*0201) are better than those between pigs and mice (H-2Db/H-2Kb). The comparison also indicates that the amino acid residues critical for recognition by human KIRs are altered in the swine class I molecules. The amino acids responsible for binding human CD8 coreceptor are largely conserved although there are two critical residues substituted. A functional test indicated that the human T cells specific for the prokaryotically expressed SLA P1protein could respond quite well in vitro to the class I-positive swine chondrocytes and PBMCs in presence of human APCs. This implies that, due to the substitution of two critical residues, the inaccessibility of human CD8 coreceptor to swine class I molecule might be contributable to the indirect pathway that the human T cells have to use for recognizing the SLA class I xenogeneic antigens.

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A binding site for the T-cell co-receptor CD8 on the α3 domain of HLA-A2

Cited by 490 publications

References 48 publications

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules

Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes

Novel SLA class I alleles of Chinese pig strains and their significance in xenotransplantation

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