The identification of CD4(+) T-cell epitopes is a laborious and tedious pro
cess. Various computer-assisted algorithms have been designed to assist in
this process by predicting potential MHC-binding epitopes. Recently, the no
vel approach of using soluble MHC class II tetramers as a tool to identify
T-cell epitopes has been developed successfully. We show that the T-cell ep
itopes identified using MHC tetramers are also predicted by a computer-assi
sted algorithm to bind to the same MHC molecule. We propose that epitope ma
pping using the MHC-tetramer-guided approach, in conjunction with predictiv
e computer algorithms, will allow the rapid identification of T-cell epitop
es from large proteins.