T cells are central to immunity in malaria. CD4+ helper
T
cells favour the generation of high-affinity antibodies that are
effective against blood stages and they are necessary to establish
immunological memory. The intrahepatic stage of
infection can be eliminated by specific CD8+
cytotoxic T cells (CTL). Cytokines secreted by CD4+ T cells
may also
contribute to liver stage immunity. Evolution has selected varied
mechanisms in pathogens to avoid recognition by T cells.
T cells recognize foreign epitopes as complexes with host major
histocompatibility (MHC) molecules. Thus, a simple
form of evasion is to mutate amino acid residues which allow binding to
an MHC allele. Recently, more sophisticated
forms of polymorphic evasion have been described. In altered peptide
ligand (APL) antagonism, the concurrent presentation
of particular closely related epitope variants can prevent memory T cell
effector functions such as cytotoxicity, lymphokine
production and proliferation. In immune interference, the effect
of the
concurrent presentation of such related epitope
variants can go a step further and prevent the induction of memory T cells
from naive precursors. The analysis of immune
responses to a protein of P. falciparum, the circumsporozoite
protein
(CSP), indicates that the malaria parasite may utilize these evasion strategies.
Changes in the strength of co-stimulation through the B7/CD28 pathway alter functional T cell responses to altered peptide ligands