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E F Reed

Publications and source records attributed to E F Reed.

28 records · Page 2Linked to original sources
PubMed1994

Influence of HLA class I and class II antigens on the peripheral T-cell receptor repertoire.

Using TCR-specific mAbs, we analyzed the TCR distribution in the CD4 and CD8 compartments of peripheral blood T cells from members of six families, including two which were informative for an HLA-B/DR crossover. TCR distribution in the CD4 compartment is influenced by MHC class II antigens as it was similar in the child carrying the HLA-B/DR recombination and in the HLA-DR-identical sibling. There was also a relatively small degree of difference between TCR distribution in the CD8 compartment of a child with an HLA-B/DR crossover and his HLA class-I-identical sibling. Analysis of TCR V beta gene usage in the CD4 compartment of unrelated individuals sharing an HLA-DR allele showed an increased usage of V beta 8a and V beta 12a in DR4-positive subjects. These data suggest that studies of TCR V beta gene usage in individuals with HLA-associated autoimmune diseases may provide further information about MHC-dependent biases in the T-cell repertoire.

CD4-Positive T-Lymphocytes↗
PubMed1994

RFLP characterization of the upstream regulatory region of the HLA-DQA1 gene.

We have performed population and family studies of the distribution of DNA restriction length polymorphisms (RFLPs) in the 5' region of the HLA-DQA1 gene using a probe which corresponds to a sequence of the 5' flanking region of HLA-DQA1. Southern analysis detected four polymorphic fragments (X1, X2, X3 and X4) with XbaI and three fragments (E1, E2 and E3) with EcoRI. Family segregation studies showed that these RFLPs segregated in cis with the parental HLA haplotypes. Analysis of haplotypic associations of the X and E polymorphisms with each other and with HLA-DQA1 alleles demonstrates that DQA1 alleles can be further subtyped according to the particular XE combination which they carry. Hence, definition of these alleles provides new markers for HLA haplotyping and allows further splitting of otherwise identical DQA1 alleles. This information may be helpful for studies of association of disease susceptibility and autoimmunity with HLA haplotypes.

Alleles↗
PubMed1993

Naturally processed cytokine-derived peptide bound to HLA-class II molecules.

Sequence analysis of HLA-class II (HLA-DR beta 1-1502 and 1104)-bound self-peptides from a transformed B cell line was performed. The sequences of naturally processed self-peptides bound to HLA-DR2 and DR5 were compared with protein and nucleic acid data bases for homology to known precursor proteins. Of the matches to known precursors, one peptide showed 100% homology to the third framework and CDR3 regions of Ig VH expressed by the line. Another peptide matched 100% to the human equivalent of macrophage inflammatory protein (MIP). A synthetic peptide corresponding to the naturally processed form of MIP (KPGVIFLTKRSRQV) was shown to inhibit Ag-specific HLA-DR beta 1*1104-restricted T cell proliferation. This indicates that the MIP peptide binds to HLA-DR beta 1*1104. The MIP peptide belongs to a set of peptides that showed uniform NH2-terminal processing. In this set, proline always occurred as the second residue followed by a basic lysine or arginine in position nine. This suggests that final NH2-terminal processing of peptides precedes their binding to MHC molecules. A distinct, second set of peptides showed ragged NH2-terminii, as has been reported for other naturally processed MHC-class II-bound self-peptides.

Amino Acid Sequence↗
PubMed1993

Limited usage of T cell receptor V beta genes by allopeptide-specific T cells.

T cell reactivity to alloantigens results from direct and indirect recognition of allogeneic MHC molecules and/or peptides. Although direct recognition is not self-MHC restricted, indirect recognition, the result of alloantigen processing and presentation by host APC, is restricted by the self (responder) MHC molecule to which the allopeptide has bound. We have studied the MHC restriction and TCR usage in T cell alloreactivity to a synthetic peptide corresponding to amino acid residues 21-42 of the DR beta 1*0101 molecule. T cell lines were developed by in vitro immunization of T cells from three responders carrying the DR beta 1*1101 allele with this peptide. In all three responders, reactivity to peptide 21-42 was restricted by the DR11 molecule. A limited usage of V beta genes was found in these T cell lines, all of which shared the expression of V beta 13.2. Because indirect recognition of allopeptide may play an important role in chronic, antibody-mediated allograft rejection, study of the TCR gene usage may contribute to the development of specific immunosuppression therapy.

Antibodies, Monoclonal↗
PubMed1993

Differentiation-stage specific self-peptides bound by major histocompatibility complex class I molecules.

We have tested the hypothesis that phenotypic changes of development are accompanied by expression of differentiation-stage specific peptides bound to major histocompatibility complex (MHC) class I molecules. The U937 cell line, when cultured in the presence of phorbol myristate acetate (PMA), undergoes differentiation from monoblasts to macrophage-like cells. The high-performance liquid chromatography profile of peptides eluted from purified human histocompatibility leukocyte antigen class I molecules expressed by U937 treated with PMA differs from that obtained from control, untreated U937 cells. Chemical sequencing of eluted peptides identified a peptide derived from cytomegalovirus in both treated and untreated cells. PMA-treated, but not untreated cells, displayed an additional peptide derived from interleukin 1 beta. Hence, differentiation-induction of U937 is accompanied by the presentation of at least one differentiation-stage specific peptide. Our results indicate that, similar to viral infection, cellular development and transformation is accompanied by the de novo synthesis of proteins which are processed and presented on MHC class I molecules.

Amino Acid Sequence↗
PubMed1993

Major histocompatibility complex-restricted recognition of autologous chronic lymphocytic leukemia by tumor-specific T cells.

From the peripheral blood of a patient with chronic lymphocytic leukemia (CLL) we generated a T-cell line and clones which recognized autologous CLL. The line comprised T-cell clones which responded to the CLL as well as to autologous Epstein-Barr virus (EBV)-transformed B cells in an HLA-DR-restricted fashion. In addition, the line comprised clones which were CLL-specific and showed no reactivity against EBV-transformed B cells and against autologous peripheral blood mononuclear cells obtained during remission. The proliferative response of the CLL-specific T-cell clone was inhibited by monoclonal antibodies to HLA-DR11, the major histocompatibility complex (MHC)-restrictive element. These results indicate that the MHC class-II molecule of CLL binds a tumor-specific peptide which is recognized by autologous T cells in an MHC class-II-restricted fashion. Such a peptide may serve as a target for immunotherapy.

Amino Acid Sequence↗