**Core Concept**
HLA (Human Leukocyte Antigen) plays a crucial role in the immune system, particularly in graft rejection. The HLA system is a group of genes that code for proteins responsible for the regulation of the immune response, ensuring that the body's immune system can distinguish between its own cells and foreign substances. In the context of organ transplantation, HLA matching between the donor and recipient is essential to minimize the risk of graft rejection.

**Why the Correct Answer is Right**
Graft rejection occurs when the immune system recognizes the transplanted organ as foreign and mounts an immune response against it. The primary HLA class involved in graft rejection is HLA class II. HLA class II molecules are expressed on the surface of antigen-presenting cells, such as dendritic cells and B cells, and present peptide fragments from outside the cell to T cells. In graft rejection, HLA class II molecules on the transplanted organ are recognized as foreign by the recipient's immune system, triggering an immune response against the graft.

**Why Each Wrong Option is Incorrect**
**Option A:** HLA class I is primarily involved in presenting endogenously synthesized peptides to CD8+ T cells. While HLA class I can also play a role in graft rejection, it is not the primary class involved.
**Option B:** HLA class III molecules are involved in the complement system and cytokine production but are not directly involved in graft rejection.
**Option C:** HLA class I and II molecules are both involved in graft rejection, but HLA class II is the primary class involved in presenting exogenously derived peptides to CD4+ T cells.

**Clinical Pearl / High-Yield Fact**
In organ transplantation, HLA matching between the donor and recipient is critical to minimize the risk of graft rejection. The higher the degree of HLA matching, the lower the risk of graft rejection and the better the graft survival rate.

**Correct Answer:** C. HLA class II.