Novel monoclonal antibodies against mouse NK cell receptors
General Material Designation
[Thesis]
First Statement of Responsibility
L. Corral
Subsequent Statement of Responsibility
D. H. Raulet
.PUBLICATION, DISTRIBUTION, ETC
Name of Publisher, Distributor, etc.
University of California, Berkeley
Date of Publication, Distribution, etc.
1997
PHYSICAL DESCRIPTION
Specific Material Designation and Extent of Item
114
DISSERTATION (THESIS) NOTE
Dissertation or thesis details and type of degree
Ph.D.
Body granting the degree
University of California, Berkeley
Text preceding or following the note
1997
SUMMARY OR ABSTRACT
Text of Note
Natural killer (NK) cells mediate the lysis of tumor cells, virally infected cells and bone marrow cell grafts. Whether these cells are killed by NK cells depends on a delicate balance between NK cell activating and inhibitory receptors. It has been demonstrated that cells with little or no cell surface expression of major histocompatibility complex (MHC) class I molecules are susceptible to NK cell lysis. However, there are MHC class I-deficient cells that are not lysed by NK cells. This indicates that additional activating signals may be required to induce NK cell lysis. NK cell activating receptors have not been very well characterized. To identify NK cell activating receptors that might be involved in tumor cell lysis, monoclonal antibodies (mAbs) were made in Syrian hamsters. Four mAbs generated were selected for further study. Two of the mAbs, 14B11 and 2F1, were specific for NK cells while the other two mAbs stained NK and T cells. The focus of this dissertation is on 14B11 and 2F1 mAbs. 14B11 mAb recognizes both Ly49C and Ly49I, MHC class I-specific inhibitory receptors expressed on NK cells. 14B11 mAb recognizes at least one other receptor which is expressed on NK cells in B6/B10 MHC cogenic mice but is difficult to detect in other mouse strains. Redirected lysis experiments indicate that the additional receptor recognized by 14B11 mAb may be an activating receptor since the addition of 14B11 mAb to activated NK cells augmented the lysis of target cells. The mouse homolog of MAFA (mast-cell function-associated antigen) is recognized by 2F1 mAb. MAFA was reported to inhibit the Fcusd\varepsilonusdRI stimulation-induced mast cell secretory response in rats. The function of MAFA on mouse NK cells remains to be determined. Nevertheless, the 2F1 antigen appears to be expressed in an MHC class I-dependent manner. Moreover, the 2F1 antigen is expressed less frequently, and at lower levels by NK cells in MHC class I-deficient mice suggesting an important role for the 2F1 antigen on NK cells.