Molecular Aspects of the Processing and Presentation of Avidin by Macrophages to T Lymphocytes

Abstract

The unmatched affinity of avidin for binding to biotin (1) provides a unique tool for tracing and characterizing the structure of the avidin molecule during cellular processing and presentation. Accordingly, we have undertaken studies using avidin as an antigen, the results of which support the following conclusions

• 1. Ir genes regulating T cell immune responses to avidin map to I-A and are Reflected in marked differences between high (I-A ^{s, b, d}) and low responders (I-A^k) (Table 1).

• 2. After uptake and processing by macrophages avidin becomes 1000-fold more potent in stimulating proliferation of anti-avidin T lymphocytes.

• 3. The molecular differences between processed avidin and native avidin involve breakdown into monomeric or smaller fragments and changes in sugar moieties. Avidin degraded to the point at which it will no longer bind biotin will not activate T lymphocytes. Thus, conservation of three-dimensional integrity of the molecule is correlated ith its antigenicity for anti-avidin T lymphocytes.

• 4. Processed avidin is reversibly complexed with an H-2 restriction moiety originating from the macrophages. The complex itself can activate anti-avidin lines of T lymphocytes free of antigen-presenting cells. Such lines, without added macrophages, will not respond to native avidin or to processed avidin that is not complexed. Avidin primed lymph node cells, in contrast, will respond to processed avidin that is not complexed to the H-2 restriction element.

• 5. Macrophages from Ir gene high or low responder mice are indistinguishable in their up-take and processing of avidin. The differences in Ir phenotype appear to be related to the population of T lymphocytes to which the processed antigen is addressed by its complexing with the restriction moiety.