CD28 (Cluster of Differentiation 28) is a homodimeric stimulatory cell surface receptor of the immunoglobulin (Ig) superfamily that is located on the chromosome 2q33.2. It is expressed on naive T cells and has also been found on the surface of plasma cells, eosinophils, and neutrophils. CD28 remains the most extensively studied costimulatory molecular and is a primary one for T-cell activatio. The control of T-cell responses through CD28 co-stimulation provides a means of anti-self and antimicrobial immunity. CD28 is essential for the lymphocyte activation and survival. A number of antigen-experienced T-cells lose CD28, and then can be re-activated without its engagement. Diseases linked to CD28 involve mycosis fungoides and Sezary's disease and the related pathways are Th2 differentiation pathway and RET signaling. CSPG4 (Chondroitin sulfate proteoglycan 4), also known as MCSP (Melanoma-associated chondroitin sulfate proteoglycan), NG2 (Neuron-glial antigen 2) or gp 240, is a unique glycoprotein-proteoglycan complex that in humans is encoded by the gene CSPG4. It is regarded as a well-characterized melanoma cell-surface antigen and involved in numerous aspects of melanoma cell biology. NG2 is the protein with a 250 kDa core glycoprotein which the more than 450 kDa proteoglycan component is attached to. Except human melanomas, this anti-tumor target antigen is still expressed on other tumors including gliomas, neuroblastomas, breast carcinomas, and acute leukemias. And it plays an essential role in tumor cell invasion, migration, and angiogenesis.