Functional differences between monocyte chemotactic protein-1 receptor A and monocyte chemotactic protein-1 receptor B expressed in a Jurkat T cell

monocyte chemotactic protein-1 (MCP-1) receptor (MCP-1R) is expressed on mo nocytes, a subpopulation of memory T lymphocytes, and basophils, Two altern atively spliced forms of MCP-1R, CCR2A and CCR2B, exist and differ only in their carboxyl-terminal tails. To determine whether CCR2A and CCR2B recepto rs function similarly, Jurkat T cells were stably transfected with plasmids encoding the human CCR2A or CCR2B gene. Nanomolar concentrations of MCP-1 induced chemotaxis in the CCR2B transfectants that express high, intermedia te, and low levels of MCP-1R. Peak chemotactic activity was shifted to the right as receptor number decreased. Five-fold more MCP-1 was required to in itiate chemotaxis of the CCR2A low transfectant, but the peak of chemotaxis was similar for the CCR2A and CCR2B transfectants expressing similar numbe rs of receptors. MCP-1-induced chemotaxis was sensitive to pertussis toxin, implying that both CCR2A and CCR2B are G(i)alpha protein coupled. MCP-1 in duced a transient Ca2+ flux in the CCR2B transfectant that was partially se nsitive to pertussis toxin, In contrast, MCP-1 did not induce Ca2+ flux in the CCR2A transfectant. Since MCP-1 can stimulate chemotaxis of the CCR2A t ransfectant without inducing Ca2+ mobilization, Ca2+ flux may not be requir ed for MCP-1-induced chemotaxis in the Jurkat transfectants. These results indicate that functional differences exist between the CCR2A and CCR2B. tra nsfectants that can be attributed solely to differences in the carboxyl-ter minal tail.