Identification of a tap-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen

Aldrich, Carla J.; DeCloux, Amy; Woods, Amina S.; Cotter, Robert J.; Soloski, Mark J.; Forman, James

doi:10.1016/0092-8674(94)90550-9

Cited by 260 publications

(218 citation statements)

References 55 publications

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“…In the mouse, the CD94/ NKG2A heterodimer interacts with the class Ib molecule Qa-1 b in complex with leader peptides from some class Ia allotypes such as H-2D b [11,12]. Members of the human killer cell immunoglobulin receptor (KIR) family bind to different allotypes of HLA class Ia [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2

et al. 2010

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Missing-self-reactivity can be mimicked by blocking self-specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab-mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self-tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H-2 b ) NK cells were blocked with F(ab') 2 fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence-labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK celldependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rejection was maintained after treatment with 5E6 F(ab') 2 for 9 wk, arguing against the induction of NK cell anergy or autoreactivity during this time. Combination therapy using 5E6 F(ab') 2 together with high dose IL-2 treatment further increased lymphoma cell rejection. In addition, combination therapy reduced growth of melanoma cell line tumors established by s.c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I-expressing tumors.

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Section: Introductionmentioning

confidence: 99%

In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2

et al. 2010

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“…Recognition of Qa-1 b by alloreactive CTL was dependent on the presence of a H-2D-linked gene referred to as the Qa-1 determinant modifier (Qdm) (23). Qdm was subsequently identified as a nonamer peptide (AMAPRTLLL) derived from residues 3-11 of the leader peptide present in most H-2D proteins (27). Peptide elution studies subsequently demonstrated that Qdm was the dominant peptide associated with Qa-1 b (28).…”

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confidence: 99%

A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b

Sullivan

Vivian

et al. 2012

The Journal of Immunology

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The primary function of the monomorphic MHC class Ib molecule Qa-1b is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1b function is unclear. We have assessed the interaction between Qa-1b and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1b bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1b. Whereas the Qa-1b-AMAPRTLLL complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1b was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1b and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1b and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1b with CD94-NKG2 receptors.

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“…The Qa-1 b -restricted CTL clones D5D2 and 39.1D7X were described previously (1,37). Clone D5D2 recognizes the Qdm peptide and other peptides that are very similar in sequence to it, including the D k variant (AMVPRTLLL).…”

Section: Cell Lines and Transfectantsmentioning

confidence: 99%

“…The mixture was air dried in a dark chamber at room temperature, and the sample was inserted into the mass spectrometer. The ions obtained were mass analyzed using time-of-flight mass spectrometry (1). Guanidination was performed by adding 1 l of a specific lyophilized HPLC fraction, which had been resuspended at one-tenth the original volume in water, to 1 l 6 M O-methylisourea at pH 11.…”

Section: Mass Spectrometrymentioning

confidence: 99%

A Peptide from Heat Shock Protein 60 Is the Dominant Peptide Bound To Qa-1 in the Absence of the MHC Class Ia Leader Sequence Peptide Qdm

Davies¹,

Kalb

Liang

et al. 2003

The Journal of Immunology

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The MHC class Ib molecule Qa-1 binds specifically and predominantly to a single 9-aa peptide (AMAPRTLLL) derived from the leader sequence of many MHC class Ia proteins. This peptide is referred to as Qdm. In this study, we report the isolation and sequencing of a heat shock protein 60-derived peptide (GMKFDRGYI) from Qa-1. This peptide is the dominant peptide bound to Qa-1 in the absence of Qdm. A Qa-1-restricted CTL clone recognizes this heat shock protein 60 peptide, further verifying that it binds to Qa-1 and a peptide from the homologous Salmonella typhimurium protein GroEL (GMQFDRGYL). These observations have implications for how Qa-1 can influence NK cell and T cell effector function via the TCR and CD94/NKG2 family members, and how this effect can change under conditions that cause the peptides bound to Qa-1 to change.

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Identification of a tap-dependent leader peptide recognized by alloreactive T cells specific for a class Ib antigen

Cited by 260 publications

References 55 publications

In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2

In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2

A Structural Basis for Antigen Presentation by the MHC Class Ib Molecule, Qa-1b

A Peptide from Heat Shock Protein 60 Is the Dominant Peptide Bound To Qa-1 in the Absence of the MHC Class Ia Leader Sequence Peptide Qdm

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