Expression of MIF and CD74 in leukemic cell lines: correlation to DR expression destiny
Insights
Invariant chain (CD74) and macrophage migration inhibitory factor (MIF) play roles in immune escape. Their interaction influences antigen presentation, impacting immune surveillance in leukemia.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Invariant chain (CD74) is a glycoprotein chaperone for MHCII molecules and a receptor for macrophage migration inhibitory factor (MIF).
- CD74 and MIF are implicated in immune surveillance and escape mechanisms.
- Leukemic cells utilize various strategies to evade immune detection.
Purpose of the Study:
- To investigate the roles of CD74 and MIF in immune surveillance escape.
- To analyze the expression and secretion of MIF and CD74 in different leukemia cell lines.
- To elucidate the interaction between CD74, MIF, and HLA-DR in the context of antigen presentation.
Main Methods:
- Flow cytometry was used to detect MIF and CD74 expression and secretion.
- Leukemia cell lines (HL-60, Raji, K562) and primary pre-B leukemic cells were analyzed.
- Gene transfection techniques were employed to study the effects of HLA-DOα and HLA-DOβ expression.
Main Results:
- Leukemic cells exhibited high intracellular/membrane CD74 and MIF expression.
- MIF secretion was inversely correlated with intracellular HLA-DR expression.
- IFN-γ modulated MIF expression and secretion in specific cell lines.
- CD74 co-precipitation with HLA-DOβ inhibited MIF/HLA-DR binding.
- Induced HLA-DOα expression decreased MIF levels and increased HLA-DR surface expression.
Conclusions:
- CD74 and MIF are involved in the immune surveillance escape of leukemic cells.
- The interaction between CD74, MIF, and HLA-DO molecules influences antigen presentation.
- MIF may play a role in the antigen presentation process, potentially contributing to immune evasion in leukemia.
Abstract:
Invariant chain (Ii) or CD74 is a non-polymorphic glycoprotein, which apart from its role as a chaperone dedicated to MHCII molecules, is known to be a high-affinity receptor for macrophage migration inhibitory factor (MIF). The present study aimed to define the roles of CD74 and MIF in the immune surveillance escape process. Towards this direction, the cell lines HL-60, Raji, K562 and primary pre-B leukemic cells were examined for expression and secretion of MIF. Flow cytometry analysis detected high levels of MIF and intracellular/membrane CD74 expression in all leukemic cells tested, while MIF secretion was shown to be inversely proportional to intracellular HLA-DR (DR) expression. In the MHCII-negative cells, IFN-γ increased MIF expression and induced its secretion in HL-60 and K562 cells, respectively. In K562 cells, CD74 (Iip33Iip35) was shown to co-precipitate with HLA-DOβ (DOβ), inhibiting thus MIF or DR binding. Induced expression of DOα in K562 (DOα-DOβ+) cells in different transfection combinations decreased MIF expression and secretion, while increasing surface DR expression. Thus, MIF could indeed be part of the antigen presentation process.
