Nature of T Lymphocyte Recognition of Macrophage-Associated Antigens

Abstract

The immune response of strain 2, strain 13, and (2 × 13)F₁ guinea pigs was studied after immunization with human fibrinopeptide Bβ(hFPB), a 14 amino acid (Bβ1-14) thrombin-derived fragment of fibrinogen. Several weeks after immunization, strain 2 and (2 × 13)F₁ antimals showed a positive anti-hFPB delayed-type hypersensitivity skin test and produced a dramatic hFPB-specific T lymphocyte proliferative response in vitro, as assessed by the incorporation of ³H-thymidine. Strain 13 animals immunized with hFPB did not produce an anti-hFPB skin test and showed little or no in vitro T cell proliferation with hFPB. Neither guinea pig strain produced detectable anti-hFPB antibody as determined by radioimmunoassay. Immune T cells were also tested for their ability to respond to several sequential synthetic homologues of hFPB. Strain 2 and (2 × 13)F₁ T cells immunized with hFPB (Bβ1-14) were stimulated by fragments Bβ3–14, 5–14 and 7–14, but not by fragments Bβ1–13 and 9–14. In addition, strain 2 and strain 13 guinea pigs were immunized with the various homologues themselves and the immune T cells tested for responsiveness in vitro with hFPB and a battery of the fragments. Strain 2 T cells immunized with Bβ1–13 showed no proliferative response with Bβ1–14, 3–14, 5–14 and 7–14, and neglible stimulation with the homologous antigen Bβ1–13. After immunization with Bβ5–14 and 7–14, strain 2 T cells showed a proliferative response with Bβ1–14, 3–14, 5–14, and 7–14, but not with Bβ1–13. T cells from strain 2 animals immunized with B 9–14 were unresponsive with all homologues tested. T cells from strain 13 guinea pigs immunized with Bβ1–13 produced a dramatic proliferative response with Bβ1–13, but were unresponsive with Bβ1–14, 3–14, 5–14, and 7–14. Strain 13 animals immunized with Bβ5–14 and 9–14 showed no T cell response with any of the homologues tested, whereas Bβ7–14 immune strain 13 T cells produced a small response with Bβ7–14. These results are discussed with respect to T cell recognition of specific amino acid sequences of the fibrinopeptide molecule.