Abstract:
:The efficacy of cytotoxic T lymphocytes (CTL) has been shown to be highly dependent upon their functional avidity (the sensitivity of their cellular response to MHC-peptide complexes). To examine this relationship, we employed target cell lysis as a quantitative measure and established a set of four CTL clones that exhibited a range of functional avidities spanning more than three orders of magnitude. Within this set, clones displayed a linear correlation between functional avidity and the TCR down-regulation that occurred in response to increasing antigen density. Staining intensity of MHC-peptide tetramer, however, correlated only with the very highest and very lowest avidity clones; the two intermediate-avidity clones showed an inverse relationship between tetramer staining and functional avidity. Compensation for differences in surface levels of TCR improved the correlation, but failed to fully account for this discrepancy. Comparison of TCR signals generated by stimulation of CTL with substrate-bound soluble MHC-peptide or antigen-presenting cells suggested that internal TCR signaling efficiency accounts for at least a portion of the observed functional avidity and suggests the need for caution in directly relating tetramer staining to avidity.
journal_name
Int Immunoljournal_title
International immunologyauthors
Derby MA,Wang J,Margulies DH,Berzofsky JAdoi
10.1093/intimm/13.6.817subject
Has Abstractpub_date
2001-06-01 00:00:00pages
817-24issue
6eissn
0953-8178issn
1460-2377journal_volume
13pub_type
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