PT  - JOURNAL ARTICLE
AU  - De La Cruz, V F
AU  - Maloy, W L
AU  - Miller, L H
AU  - Good, M F
AU  - McCutchan, T F
TI  - The immunologic significance of variation within malaria circumsporozoite protein sequences.
DP  - 1989 May 15
TA  - The Journal of Immunology
PG  - 3568--3575
VI  - 142
IP  - 10
4099  - http://www.jimmunol.org/content/142/10/3568.short
4100  - http://www.jimmunol.org/content/142/10/3568.full
SO  - J. Immunol.1989 May 15; 142
AB  - We have previously suggested that variation within the circumsporozoite protein of the malaria parasite Plasmodium falciparum was the result of selection by immune T cells. Our hypothesis has been supported by experiments documenting a lack of cross-reactivity between variant peptides from the C-terminal region for murine T cells primed by 7G8-specific sequences. Now, by using a murine model we have found that peptides representing variant regions (amino acid residues 326-343 and 361-380) of two other parasite clones (Wel and LE5) are also immunodominant for murine T cells. However, there were distinct changes in response profiles. For example, whereas lymph node cells from H-2d and H mice immunized with peptides from the 326-343 region of all three variants proliferated in vitro after homologous challenge, only lymph node cells from H-2b mice immunized with LE5 peptide proliferate after homologous challenge. In contrast, only LE5 did not induce lymphoproliferation against homologous challenge in the H-2s background. These data suggest that the naturally occurring substitutions affect agretopic (i.e., Ia). Peptides from all variants representing the 361-380 domain were recognized only by T cells from H-2k mice. Also, in nearly all cases, T cells primed by one sequence did not recognize variant sequences. The immunodominance of these domains from three different clones and the lack of significant cross-reactivity further supports the hypothesis that variation is the result of T cell immune pressure.