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D Elferink

Publications and source records attributed to D Elferink.

7 recordsLinked to original sources
PubMed1995

DR4Dw4/DR53 molecules contain a peptide from the autoantigen calreticulin.

Rheumatoid arthritis (RA) occurs more frequently in HLA-DR4+ individuals than in those who do not express this MHC class II molecule. Although the role of this genetic factor in the immunopathology of this autoimmune disease is unclear, the association of RA with HLA-DR4 may indicate that DR4 molecules present autoantigen(s) to T cells. Here we report the analysis of naturally processed peptides, eluted from a mixture of HLA-DR4Dw4 (DRB1*0401) and DR53 (DRB4*0101) molecules isolated from an RA patient-derived EBV-transformed B cell line. Several (size variants of) self-peptides originating from the autologous molecules HLA-A2, HLA-Cw9, HLA-B62, HLA-DR4Dw4 and HLA-DR53, were identified. We also found a sequence that has no homology to any protein in the SwissProt protein sequence databank, and a peptide identical to an internal fragment of the autoantigen calreticulin. The association of the identified peptides with cells expressing HLA-DR4Dw4/DR53 was confirmed by peptide binding analysis. In agreement with previously described peptide binding motifs for DR4Dw4, most peptides contained an aromatic residue (Phe, Tyr, Trp) at relative position i and a small hydroxyl-containing residue (Ser, Thr) at i + 5. Our findings indicate that in RA patient-derived EBV-transformed B cells DR4Dw4/DR53 molecules present a peptide from the autoantigen calreticulin. Interestingly, autoantibodies against calreticulin have been found in various rheumatic diseases, including rheumatoid arthritis. Thus, the analysis of HLA class II-bound peptides can lead to the identification of putative T helper epitopes, which might be involved in the immunopathology of autoimmune diseases.

Amino Acid Sequence↗
PubMed1987

Deficiency of immunity to Mycobacterium avium that can be restored by allogeneic lymphocytes.

A 3-year-old girl developed a disseminated Mycobacterium avium infection despite treatment with eight antimycobacterial drugs. She had no pre-existent general humoral or cellular immunodeficiency. In the course of the disease B lymphocyte areas in the lymphoid tissues were replaced by histiocytes and an IgM and IgA deficiency evolved. The patient still made antibodies to concomitant micro-organisms and to transfused blood cells. Peripheral blood mononuclear cells (PBMC) had normal responses to mitogens and various antigens in vitro. However, she lacked any response to mycobacterial antigens, in vivo and in vitro. The defect appeared not to be dependent on immunosuppression by lymphocytes or monocytes or on deficient antigen presentation by monocytes. because a genetic origin could not be substantiated, acquired immunological paralysis for mycobacterial antigens was the most likely explanation. Addition of irradiated PBMC from her HLA-A, -B, -C and -DR phenotypically identical father, transferred a response to mycobacterial antigens of the patient's PBMC in vitro. We concluded that the disseminated M. avium infection was accompanied by a selective deficiency of the lymphocyte response to mycobacterial antigens which could be restored by allogeneic antigen responsive lymphocytes.

Antigens, Bacterial↗
PubMed1986

Quantitative and qualitative differences in HLA-DR molecules correlated with antigen-presentation capacity.

The monoclonal antibodies 7.3.19.1 (anti-DRw52-like) and B8.11.2 (anti-DR framework) were used for the isolation and characterization of HLA class II molecules expressed by HLA-DR3 and DR5 homozygous B cell lines. Sequential immunoprecipitation studies demonstrated that from these cells class II molecules can be isolated which are characterized by the presence or absence of DR framework (DR) and DRw52-like (DRw62) determinants: (DR+, DRw52+), (DR+, DRw52-) and (DR-, DRw52+). The DR3 donor cells appeared to express only the (DR+, DRw52+) and (DR-, DRw52+) class II molecules whereas DR5-positive cells express only the (DR+, DRw52+) and (DR+, DRw52-) class II molecules. Besides qualitative differences some of the above-mentioned molecules appeared to differ in their levels of expression. To investigate whether this might have functional implications, cells with the HLA-DR3 and -5 haplotypes were used to present antigen purified protein derivative of tuberculin (PPD) to PPD-specific T cell lines and the blocking capacity of the two monoclonal antibodies 7.3.19.1 and B8.11.2 was determined. A remarkable correlation was observed between the type of class II molecule blocked by these monoclonal antibodies and its quantitative expression. However, (DR-, DRw52+) molecules, clearly expressed by DR3 cells, were not involved in the presentation of PPD. This indicates that not only quantitative but also qualitative aspects may play a role in the selection of the type of class II molecule that will be involved in antigen presentation.

Antibodies, Monoclonal↗
PubMed1984

Proliferative response of human lymphocytes to antigens not experienced in vivo.

A comparison has been made of two methods for studying the immune response of human lymphocytes to antigens not experienced in vivo. In the first method, the sensitization-restimulation assay (or S/R test), lymphocytes from blood were sensitized to antigen in bulk cultures and then redistributed into microtiter plates for a second culture period in the presence of specific or unrelated antigen. The proliferative response of the sensitized cells in the second culture was measured by 3H-thymidine uptake. With this protocol one could strictly control the specificity of the response in the second culture by using different antigens in the sensitization and restimulation phases of the assay. An alternative method for studying the response of lymphocytes to antigens not experienced in vivo was an adaptation of the lymphocyte transformation assay by extending the time of culture for up to four days. We found that this latter assay was not appropriate for determining if individuals were nonresponders to antigens not experienced in vivo. Limiting dilution analysis showed that the frequency of antigen reactive cells was so low that nonrandom distribution of reactive cells was obtained and the frequency of reactive cells depended on the concentration of antigen used in the cultures. Further it was impossible to adequately control for the specificity of the response.

Antigens↗
PubMed1984

The immune response to (T,G)-A-L and GAT in man: an association of nonresponsiveness to (T,G)-A-L with HLA-DRw8.

The response of human lymphocytes to synthetic polypeptides has been measured by sensitizing cells in vitro followed by restimulation with the sensitizing antigen or with cross-reacting antigens. It was found that there was considerable individual heterogeneity in the specific response and the cross-reaction obtained with the antigens (T,G)-A-L, GAT, GT, and GA. In spite of this heterogeneity, it is possible to define three different response patterns using nonresponsiveness to (T,G)-A-L and the failure of (T,G)-A-L to cross-restimulate GAT sensitized cells as discriminating criteria. The nonresponders to (T,G)-A-L show a significant association with HLA-DRw8 and it is suggested that this might represent a dominant HLA associated immune response gene involved in the regulation of the response to (T,G)-A-L. We further show that the individuals whose cells respond to (T,G)-A-L form a heterogeneous group which may explain the conflicting results previously published on the genetic control of the immune response to (T,G)-A-L in man.

Antigens↗
PubMed1983

An approach to study in vitro the expression of HLA-encoded genetic factors predisposing to tuberculoid leprosy.

The existence of HLA-encoded genetic factors controlling susceptibility to tuberculoid leprosy in humans has been firmly established. Furthermore HLA-DR2 has been recognized as a marker for tuberculoid leprosy in India. At this moment, however, the gene products involved and the mechanism by which they confer susceptibility to tuberculoid leprosy remain only speculative. In an attempt to detect in vitro the expression of these HLA-encoded factors, we studied 12 tuberculoid leprosy patients and 22 healthy family members in a lymphocyte transformation test (LTT). All individuals were derived from multi-case Indian families, previously reported to show the presence of HLA-linked susceptibility genes. Although the responder-status of the healthy contact siblings was shown to behave independently from the fact whether they were HLA-identical with the patient-siblings or not, some evidence for in vitro expression of HLA-DR2 associated factors could be obtained. Nevertheless, it is concluded that the standard LTT seems not to be a test-system of first choice to detect the in vitro expression of the genes under study.

HLA Antigens↗