Abstract: The poxvirus proteins designated A41L and 130L bind to three receptor-like protein tyrosine phosphatases (RPTP), leukocyte common antigen related protein (LAR), RPTP-?, and RPTP-?, that are present on the cell surface of immune cells. When a host is infected with the poxvirus, binding of A41L to cell surface proteins on the host cells results in suppression of the immune response. The present invention provides agents such as antibodies, and antigen-binding fragments thereof, small molecules, aptamers, small interfering RNAs, and peptide-IgFc fusion polypeptides that interact with one or more of LAR, RPTP-?, and RPTP-? expressed by immune cells or interact with a polynucleotide encoding the RPTP. Also provided are RPTP Ig domain oligomers and Fc fusion polypeptides. Such agents are useful for treating an immunological disorder in a subject according to the methods described herein.