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Human helper T-cell clones that recognize different influenza hemagglutinin determinants are restricted by different HLA-D region epitopes

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Abstract

Human T-lymphocyte clones (TLCs) were generated against the hemagglutinin (HA) of A/Texas/1/77 influenza virus by limiting dilution. TLCs were then screened for antigen specificity on chemically synthesized peptides representing the HA1 molecule. It has been hypothesized that different T cells that recognize the identical antigenic determinant are controlled by (restricted by) the same class II epitope. Two TLCs, HA1.4 and HA1.7, both recognized the same HA peptide and in proliferation studies exhibited identical restriction patterns. Two other clones, HA 1.9 and HA 2.43, recognized different HA determinants and also had distinct restriction patterns. Proliferation inhibition studies with monoclonal antibodies against human class II molecules demonstrated three unique patterns of blocking with the clones, suggesting that clones may be restricted to a unique class II epitope depending on the HA determinant recognized. These data can be interpreted as supporting the argument that human immune responses to influenza hemagglutinin are under Ir gene control exerted at the level of the viral antigenic determinant recognized in association with particular D-region restricting elements. The determinant selection and clonal deletion theories are compared for their capacity to best explain these findings.

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Abbreviations

3HTdR:

tritiated methyl thymidine

MHC:

major histocompatibility complex

HLA:

human MHC

PBLs:

peripheral blood lymphocytes

APCs:

antigen-presenting cells

TLCs:

T-lymphocyte clones

TCGF:

T-cell growth factor

MoAbs:

monoclonal antibodies

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Authors and Affiliations

  1. Division of Immunologic Oncology, Vincent T. Lombardi Cancer Research Center and the Departments of Pediatrics and Microbiology, Georgetown University Medical Center, Washington, DC

    David D. Eckels, Thomas W. Sell, Sandra Rosen Bronson & Armead H. Johnson

  2. Transplantation and Immunology Branch, Naval Medical Research Institute, Bethesda, MD

    Robert J. Hartzman

  3. Imperial Cancer Research Fund, Human Tumour Immunology Unit, University College Hospital, London, England

    Jonathan R. Lamb

Authors
  1. David D. Eckels
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  2. Thomas W. Sell
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  3. Sandra Rosen Bronson
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  4. Armead H. Johnson
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  5. Robert J. Hartzman
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  6. Jonathan R. Lamb
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Eckels, D.D., Sell, T.W., Bronson, S.R. et al. Human helper T-cell clones that recognize different influenza hemagglutinin determinants are restricted by different HLA-D region epitopes. Immunogenetics 19, 409–423 (1984). https://doi.org/10.1007/BF00364644

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  • DOI: https://doi.org/10.1007/BF00364644

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